Cimzia kit cimzia Kit

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 active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older (1.3)

• Treatment of adult patients with active psoriatic arthritis. (1.4)

• Treatment of adults with active ankylosing spondylitis (1.5)

• Treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation (1.6)

Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy (1.7) 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 Polyarticular Juvenile Idiopathic Arthritis

CIMZIA is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older. 1.4 Psoriatic Arthritis

CIMZIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA). 1.5 Ankylosing Spondylitis

CIMZIA is indicated for the treatment of adults with active ankylosing spondylitis (AS).

[see

Clinical Studies (14.5)] 1.6 Non-radiographic Axial Spondyloarthritis

CIMZIA is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

[see

Clinical Studies (14.6)]. 1.7 Plaque Psoriasis

CIMZIA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy

[see

Clinical Studies (14.7)]

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria [see Warnings and Precautions (5.4)] .

The most serious adverse reactions were:

1. Serious Infections [see Warnings and Precautions (5.1)]
2. Malignancies [see Warnings and Precautions (5.2)]
3. Heart Failure [see Warnings and Precautions (5.3)]
4. Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
5. Hepatitis B Virus Reactivation [see Warnings and Precautions (5.5)]
6. Neurologic Reactions [see Warnings and Precautions (5.6)]
7. Hematologic Reactions [see Warnings and Precautions (5.7)]
8. Autoimmunity [see Warnings and Precautions (5.9)]
9. Immunosuppression [see Warnings and Precautions (5.11)]

• Serious Infections

: CIMZIA should not be initiated in patients with an active infection. Monitor for infection during and after treatment; discontinue if a serious infection develops. If invasive fungal infection develops in patients who reside or travel to regions where mycoses are endemic, consider empiric antifungal therapy. (5.1)

• Malignancies

: Cases of lymphoma and other malignancies have been observed among patients receiving TNF blockers, including CIMZIA. (5.2)

• Heart Failure

: Monitor patients for new onset or worsening congestive heart failure. (5.3)

• Hypersensitivity Reactions

: Discontinue CIMZIA and institute appropriate therapy if anaphylaxis or other serious hypersensitivity reactions 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)

• Neurologic Reactions

: Exacerbation or new onset demyelinating disease may occur; use caution in patients with pre-existing or recent-onset demyelinating disorders. (5.6)

• Hematological Reactions (including leukopenia, pancytopenia and thrombocytopenia)

: Use with caution in patients who have ongoing, or a history of, significant hematologic abnormalities. Advise patients to seek immediate medical attention if symptoms develop; consider discontinuing CIMZIA in patients with confirmed abnormalities. (5.7)

• Use with Anakinra, Abatacept, Rituximab and Natalizumab

: Increased risk of serious infections; concomitant use is not recommended. (5.8, 7.1)

• Autoimmunity

: Discontinue CIMZIA if lupus-like syndrome develops. (5.9)

• Live vaccines

: Avoid use with CIMZIA (5.10, 7.2) 5.1 Risk of Serious Infections

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 or concomitantly received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating CIMZIA and periodically during therapy.

Treatment of latent tuberculosis infection prior to therapy with TNF-blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating CIMZIA, assess if treatment for latent tuberculosis is needed; and consider an induration of 5 mm or greater a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).

Consider anti-tuberculosis therapy 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. Despite previous or concomitant treatment for latent tuberculosis, cases of active tuberculosis have occurred in patients treated with CIMZIA. Some patients who have been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated with CIMZIA. 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.

Strongly consider tuberculosis 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. During CIMZIA studies of psoriasis, malignancies (excluding non-melanoma skin cancer) were observed corresponding to an incidence rate of 0.5 (0.2, 1.0) per 100 subject-years among a total of 995 subjects who received CIMZIA. 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.

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. In the CIMZIA PsO clinical trials (placebo-controlled and open-label) there was one case of Hodgkin's 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.

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blockers, including CIMZIA. 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, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria. Some of these reactions occurred after the first administration of CIMZIA. If such reactions occur, discontinue further administration of CIMZIA and institute appropriate therapy. There are no data on the risks of using CIMZIA in patients who have experienced a severe hypersensitivity reaction towards another TNF blocker; in these patients caution is needed

[see

Adverse Reactions (6.1)].

The needle shield inside the removable cap of the CIMZIA prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex. 5.5 Hepatitis B Virus Reactivation

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 etanercept 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

Avoid use of live vaccines during or immediately prior to initiation of therapy with CIMZIA. Update immunizations in agreement with current immunization guidelines prior to initiating CIMZIA therapy.

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.

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 to opalescent, 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.

Laboratory Tests

: May cause erroneously elevated aPTT results. (7.3) 7.1 Use with Anakinra, Abatacept, Rituximab, and Natalizumab

An increased risk of serious infections has been seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit. Formal drug interaction studies have not been performed with rituximab or natalizumab. Because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA in these combinations. There is not enough information to assess the safety and efficacy of such combination therapy. Therefore, the use of CIMZIA in combination with anakinra, abatacept, rituximab, or natalizumab is not recommended

[see

Warnings and Precautions (5.8)]. 7.2 Live Vaccines

Avoid use of live (including attenuated) vaccines during or immediately prior to initiation of therapy with CIMZIA

[see

Warnings and Precautions (5.10)]. 7.3 Laboratory Tests

Interference with certain coagulation assays has been detected in patients treated with CIMZIA. Certolizumab pegol may cause erroneously elevated activated partial thromboplastin time (aPTT) assay results in patients without coagulation abnormalities. This effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL APTT-SP liquid and HemosIL lyophilized silica tests from Instrumentation Laboratories. Other aPTT assays may be affected as well. Interference with thrombin time (TT) and prothrombin time (PT) assays has not been observed. There is no evidence that CIMZIA therapy has an effect on

in vivo

coagulation.