Cimzia Drug Information

Polyarticular Juvenile Idiopathic Arthritis

The recommended dose of Cimzia for patients 2 years of age and older with pJIA is based on weight as shown below. There is no dosage form for Cimzia that allows for patient self-administration for doses below 200 mg. For some patients (with body weight less than or equal to 90 kg), Cimzia 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 can be considered.

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. Step-by-step preparation and administration instructions are provided below.

Preparation and Storage If refrigerated, remove Cimzia from the refrigerator and allow the vial(s) to sit at room temperature for 30 minutes before reconstituting. Do not warm the vial in any other way. Use appropriate aseptic technique when preparing and administering Cimzia.

Reconstitute the vial(s) of Cimzia with 1 mL of Sterile Water for Injection, USP using the 20-gauge needle provided. The sterile water for injection should be directed at the vial wall rather than directly on Cimzia. Gently swirl each vial of Cimzia for about one minute without shaking, assuring that all of the powder comes in contact with the Sterile Water for Injection.

The swirling should be as gentle as possible in order to avoid creating a foaming effect. Continue swirling every 5 minutes as long as non-dissolved particles are observed. Full reconstitution may take as long as 30 minutes.

The final reconstituted solution contains 200 mg/mL and should be clear to opalescent, colorless to yellow liquid essentially free from particulates. Once reconstituted, Cimzia can be stored in the vials for up to 24 hours between F prior to injection. Do not freeze.

Administration 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. 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 the required volume of Cimzia. Replace the 20-gauge needle(s) on the syringes with a 23-gauge(s) for administration.

Inject the full contents of the syringe(s) subcutaneously, by pinching the skin of the 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.

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. If refrigerated, remove the prefilled syringe from the carton and let it warm to room temperature. Inspect the liquid in the prefilled syringe.

Discard the syringe if cloudy, discolored or contains particulates. Suitable sites for injection include the thigh or abdomen at least 2 inches away from the navel. Inject at least 1 inch from the previous site.

Do not inject into areas where the skin is tender, bruised, red or hard, or where there are scars or stretch marks. The needle shield inside the removable cap of the Cimzia prefilled syringe contains a derivative of natural rubber latex which may cause allergic reactions and should be handled with caution by latex-sensitive individuals.

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.

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.

Clinical Trials Experience

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. 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 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%). Controlled Studies with Crohn's Disease The data described below reflect exposure to Cimzia at 400 mg subcutaneous dosing in studies of patients with Crohn's disease. In controlled and uncontrolled studies, 1,564 patients received Cimzia at some dose level, of whom 1,350 patients received 400 mg Cimzia.

Approximately 55% of subjects were female, 45% were male, and 94% were Caucasian. The majority of patients in the active group were between the ages of 18 and 64. During controlled clinical studies, the proportion of patients with serious adverse reactions was 10% for Cimzia and 9% for placebo.

The most common adverse reactions (occurring in ≥ 5% of Cimzia-treated patients, and with a higher incidence compared to placebo) in controlled clinical studies with Cimzia were upper respiratory infections (e.g. nasopharyngitis, laryngitis, viral infection) in 20% of Cimzia-treated patients and 13% of placebo-treated patients, urinary tract infections (e.g. bladder infection, bacteriuria, cystitis) in 7% of Cimzia-treated patients and in 6% of placebo-treated patients, and arthralgia (6% Cimzia, 4% placebo). Other Adverse Reactions The most commonly occurring adverse reactions in controlled trials of Crohn's disease were described above. Other serious or significant adverse reactions reported in controlled and uncontrolled studies in Crohn's disease and other diseases, occurring in patients receiving Cimzia at doses of 400 mg or other doses include: Blood and lymphatic system disorders: Anemia, leukopenia, lymphadenopathy, pancytopenia, and thrombophilia.

Cardiac disorders: Angina pectoris, arrhythmias, atrial fibrillation, cardiac failure, hypertensive heart disease, myocardial infarction, myocardial ischemia, pericardial effusion, pericarditis, stroke and transient ischemic attack. Eye disorders: Optic neuritis, retinal hemorrhage, and uveitis. General disorders and administration site conditions: Bleeding and injection site reactions.

Hepatobiliary disorders: Elevated liver enzymes and hepatitis. Immune system disorders: Alopecia totalis. Psychiatric disorders: Anxiety, bipolar disorder, and suicide attempt.

Renal and urinary disorders: Nephrotic syndrome and renal failure. Reproductive system and breast disorders: Menstrual disorder. Skin and subcutaneous tissue disorders: Dermatitis, erythema nodosum, and urticaria.

Vascular disorders: Thrombophlebitis, vasculitis. Controlled Studies with Rheumatoid Arthritis Cimzia was studied primarily in placebo-controlled trials and in long-term follow-up studies. In placebo-controlled studies, the population had a median age of 53 years at entry; approximately 80% were females, 93% were Caucasian and all patients were suffering from active rheumatoid arthritis, with a median disease duration of 6.2 years.

Most patients received the recommended dose of Cimzia or higher. Table 1 summarizes the reactions reported at a rate of at least 3% in patients treated with Cimzia 200 mg every other week compared to placebo (saline formulation), given concomitantly with methotrexate. Table 1: Adverse Reactions Reported by ≥3% of Patients Treated with Cimzia Dosed Every Other Week during Placebo-Controlled Period of Rheumatoid Arthritis Studies, with Concomitant Methotrexate. 2 3 Hypertensive adverse reactions were observed more frequently in patients receiving Cimzia than in controls.

These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). Patients receiving Cimzia 400 mg as monotherapy every 4 weeks in rheumatoid arthritis controlled clinical trials had similar adverse reactions to those patients receiving Cimzia 200 mg every other week. Other Adverse Reactions Other infrequent adverse reactions (occurring in less than 3% of RA patients) were similar to those seen in Crohn's disease patients.

Polyarticular Juvenile Idiopathic Arthritis Clinical Study Cimzia has been studied in 193 patients with juvenile idiopathic arthritis (JIA) with active polyarthritis aged 2 years and older. In general, the safety profile for pediatric patients with JIA with active polyarthritis was similar to the safety profile seen in adult RA patients treated with Cimzia. Psoriatic Arthritis Clinical Study Cimzia has been studied in 409 patients with psoriatic arthritis (PsA) in a placebo-controlled trial.

The safety profile for patients with PsA treated with Cimzia was similar to the safety profile seen in patients with RA and previous experience with Cimzia. Ankylosing Spondylitis Clinical Study Cimzia has been studied in 325 patients with axial spondyloarthritis of whom the majority had ankylosing spondylitis (AS) in a placebo-controlled study (AS-1). The safety profile for patients in study AS-1 treated with Cimzia was similar to the safety profile seen in patients with RA.

Non-radiographic Axial Spondyloarthritis Clinical Study Cimzia has been studied in 317 patients with non-radiographic axial spondyloarthritis (nr-axSpA-1). Plaque Psoriasis Clinical Studies In clinical studies, a total of 1112 subjects with plaque psoriasis were treated with Cimzia. Placebo-Controlled Period (Week 0-16) In the placebo-controlled period of Studies PS-1, PS-2 and PS-3 in the 400 mg group, adverse events occurred in 63.5% of subjects in the Cimzia group compared to 61.8% of subjects in the placebo group.

The rates of serious adverse events were 4.7% in the Cimzia group and 4.5% in the placebo group. Table 2 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Cimzia group than in the placebo group. Of Cimzia-treated subjects who had elevation of liver enzymes, two subjects were discontinued from the trial.

Psoriasis-Related Adverse Events In controlled clinical studies in psoriasis, change of plaque psoriasis into a different psoriasis sub-types (including erythrodermic, pustular and guttate), was observed in <1% of Cimzia treated subjects. Adverse Reactions of Special Interest Across Indications Infections The incidence of infections in controlled studies in Crohn's disease was 38% for Cimzia-treated patients and 30% for placebo-treated patients. The infections consisted primarily of upper respiratory infections (20% for Cimzia, 13% for placebo).

The incidence of serious infections during the controlled clinical studies was 3% per patient-year for Cimzia-treated patients and 1% for placebo-treated patients. Serious infections observed included bacterial and viral infections, pneumonia, and pyelonephritis. The incidence of new cases of infections in controlled clinical studies in rheumatoid arthritis was 0.91 per patient-year for all Cimzia-treated patients and 0.72 per patient-year for placebo-treated patients.

The infections consisted primarily of upper respiratory tract infections, herpes infections, urinary tract infections, and lower respiratory tract infections. In the controlled rheumatoid arthritis studies, there were more new cases of serious infection adverse reactions in the Cimzia treatment groups, compared to the placebo groups (0.06 per patient-year for all Cimzia doses vs. 0.02 per patient-year for placebo). Serious infections included tuberculosis, pneumonia, cellulitis, and pyelonephritis.

In the placebo group, no serious infection occurred in more than one subject. There is no evidence of increased risk of infections with continued exposure over time. In controlled clinical studies in psoriasis, the incidence rates of infections were similar in the Cimzia and placebo groups.

The infections consisted primarily of upper respiratory tract infections and viral infections (including herpes infections). Serious adverse events of infection occurred in Cimzia-treated patients during the placebo-controlled periods of the pivotal studies (pneumonia, abdominal abscess, and hematoma infection) and Phase 2 study (urinary tract infection, gastroenteritis, and disseminated tuberculosis). In an open-label clinical study of 193 pediatric patients with JIA with active polyarthritis, there were 26 serious infections; the most frequently reported serious infection was pneumonia.

Tuberculosis and Opportunistic Infections In completed and ongoing global clinical studies in all indications including 5,118 Cimzia-treated patients, the overall rate of tuberculosis is approximately 0.61 per 100 patient-years across all indications. The majority of cases occurred in countries with high endemic rates of TB. Reports include cases of disseminated (miliary, lymphatic, and peritoneal) as well as pulmonary TB.

The median time to onset of TB for all patients exposed to Cimzia across all indications was 345 days. In the studies with Cimzia in RA, there were 36 cases of TB among 2,367 exposed patients, including some fatal cases. Rare cases of opportunistic infections have also been reported in these clinical trials.

In an open-label clinical study of 193 pediatric patients with JIA with active polyarthritis, opportunistic infections consisted of tuberculosis, liver tuberculosis, varicella, pneumonia fungal, and esophageal candidiasis. Two cases of disseminated tuberculosis (liver TB and disseminated TB) were fatal. Malignancies In clinical studies of Cimzia, the overall incidence rate of malignancies was similar for Cimzia-treated and control patients.

For some TNF blockers, more cases of malignancies have been observed among patients receiving those TNF blockers compared to control patients. Heart Failure In placebo-controlled and open-label studies, cases of new or worsening heart failure have been reported for Cimzia-treated patients. The majority of these cases were mild to moderate and occurred during the first year of exposure.

Hypersensitivity Reactions The following symptoms that could be compatible with hypersensitivity reactions have been reported rarely following Cimzia administration to patients: angioedema, allergic dermatitis, dizziness (postural), dyspnea, hot flush, hypotension, injection site reactions, malaise, pyrexia, rash, serum sickness, and (vasovagal) syncope. Autoantibodies In clinical studies in Crohn's disease, 4% of patients treated with Cimzia and 2% of patients treated with placebo that had negative baseline ANA titers developed positive titers during the studies. One of the 1,564 Crohn's disease patients treated with Cimzia developed symptoms of a lupus-like syndrome.

In clinical trials of TNF blockers, including Cimzia, in patients with RA, some patients have developed ANA. Four patients out of 2,367 patients treated with Cimzia in RA clinical studies developed clinical signs suggestive of a lupus-like syndrome. The impact of long-term treatment with Cimzia on the development of autoimmune diseases is unknown.

In a clinical study in pediatric patients with JIA with active polyarthritis, 17.1% of patients treated with Cimzia that had negative baseline ANA titers developed positive titers during the study. 1.1% of the patients developed anti-dsDNA antibodies during the study; no patients developed symptoms of a lupus-like syndrome.

Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of certolizumab pegol or of other certolizumab products. Patients with Crohn's disease were tested at multiple time points for antibodies to certolizumab pegol during Studies CD1 and CD2.

In patients continuously exposed to Cimzia, the overall percentage of patients who were antibody positive to Cimzia on at least one occasion was 8%; approximately 6% were neutralizing in vitro. No apparent correlation of antibody development to adverse events or efficacy was observed. Patients treated with concomitant immunosuppressants had a lower rate of antibody development than patients not taking immunosuppressants at baseline (3% and 11%, respectively).

The following adverse events were reported in Crohn's disease patients who were antibody-positive (N = 100) at an incidence at least 3% higher compared to antibody-negative patients (N = 1,242): abdominal pain, arthralgia, edema peripheral, erythema nodosum, injection site erythema, injection site pain, pain in extremity, and upper respiratory tract infection. In two long-term (up to 7 years of exposure), open-label Crohn's disease studies, overall 23% (207/903) of patients developed antibodies against certolizumab pegol on at least one occasion. The data from these two studies do not suggest an association between the development of antibodies and adverse events.

The overall percentage of patients with antibodies to certolizumab pegol detectable on at least one occasion was 7% (105 of 1,509) in the rheumatoid arthritis placebo-controlled trials. Approximately one third (3%, 39 of 1,509) of these patients had antibodies with neutralizing activity in vitro. Patients treated with concomitant immunosuppressant therapy (MTX) in RA-I, RA-II, RA-III had a lower rate of neutralizing antibody formation overall than patients treated with Cimzia monotherapy in RA-IV (2% vs. 8%).

Antibody formation was associated with lowered drug plasma concentration and reduced efficacy. In Study RA-III, too few patients developed antibodies to allow for meaningful analysis of ACR20 response by antibody status. In Study RA-IV (monotherapy), the ACR20 response was 33% versus 56%, antibody-positive versus antibody-negative status, respectively.

No association was seen between antibody development and the development of adverse events. Of the subjects who developed antibodies to certolizumab pegol, 45% (27/60) had antibodies that were classified as neutralizing. A more sensitive and drug tolerant electrochemiluminesence (ECL)-based bridging assay was used for the first time in the nr-axSpA-1 study, resulting in a greater proportion of samples having measurable antibodies to certolizumab pegol and thus a greater incidence of patients being classed as antibody positive.

In the placebo-controlled trial in patients with non-radiographic axial spondyloarthritis, after up to 52 weeks of treatment, the overall incidence of patients who were antibody positive to certolizumab pegol was 97% (248/255 patients). Of these antibody positive patients, higher titers were associated with reduced certolizumab pegol plasma levels. The data above reflect the percentage of patients whose test results were considered positive for antibodies to certolizumab pegol in an ELISA or ECL-based bridging assay, and are highly dependent on the sensitivity and specificity of the assay.

In a clinical study of pediatric patients with JIA with active polyarthritis, immunogenicity was evaluated using an ECL-based assay. For the patients receiving the recommended Cimzia dose, the incidence of treatment emergent-anti-certolizumab pegol antibody positivity was 92.4% for the entire treatment period.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Cimzia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Vascular disorder: systemic vasculitis has been identified during post-approval use of TNF blockers.

Skin: case of severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), and lichenoid skin reaction have been identified during post-approval use of TNF blockers. Immune System Disorders: sarcoidosis Neoplasms benign, malignant and unspecified (including cysts and polyps): Melanoma, Merkel cell carcinoma (neuroendocrine carcinoma of the skin).

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.

Live Vaccines

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

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.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIMZIA during pregnancy. For more information, healthcare providers or patients can contact: MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). The OTIS AutoImmune Diseases Study at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/.

Risk Summary Limited data from an ongoing pregnancy exposure registry on use of CIMZIA in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes. However, certolizumab pegol plasma concentrations obtained from two studies of CIMZIA use during the third trimester of pregnancy demonstrated that placental transfer of certolizumab pegol was negligible in most infants at birth, and low in other infants at birth (see Data ). There are risks to the mother and fetus associated with active rheumatoid arthritis or Crohn's disease.

The theoretical risks of administration of live or live-attenuated vaccines to the infants exposed in utero to CIMZIA should be weighed against the benefits of vaccinations (see Clinical Considerations ). No adverse developmental effects were observed in animal reproduction studies during which pregnant rats were administered intravenously a rodent anti-murine TNFα pegylated Fab' fragment (cTN3 PF) similar to certolizumab pegol during organogenesis at up to 2.4 times the recommended human dose of 400 mg every four weeks. The background risk of major birth defects and miscarriage for the indicated population(s) are unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with rheumatoid arthritis or Crohn's disease is correlated with maternal disease activity and that active disease increases the risk of adverse pregnancy outcomes, including fetal loss, preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) and small for gestational age birth.

Fetal/Neonatal Adverse Reaction Due to its inhibition of TNFα, CIMZIA administered during pregnancy could affect immune responses in the in utero -exposed newborn and infant. The clinical significance of BLQ or low levels is unknown for in utero -exposed infants. Additional data available from one exposed infant suggest that CIMZIA may be eliminated at a slower rate in infants than in adults (see Data ).

The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Dosing During Pregnancy and the Postpartum Period Based on a pharmacokinetic study in pregnant women with psoriasis or rheumatological diseases who were administered certolizumab pegol during pregnancy until at least 12 weeks postpartum, plasma certolizumab pegol concentrations throughout pregnancy were within the range observed in non-pregnant women with the same chronic inflammatory diseases. No dosage adjustment is required for pregnant women.

Data Human Data A limited number of pregnancies have been reported in an ongoing pregnancy exposure registry. Due to the small number of CIMZIA-exposed pregnancies with known outcomes (n=217), no meaningful comparisons between the exposed group and control groups may be conducted to determine an association with CIMZIA and major birth defects or adverse pregnancy outcomes. The last dose of CIMZIA was given on average 11 days prior to delivery (range 1 to 27 days).

Certolizumab pegol plasma concentrations were measured in samples from mothers and infants using an assay that can measure certolizumab pegol concentrations at or above 0.032 mcg/mL. Certolizumab pegol plasma concentrations measured in the mothers at delivery (range: 4.96 to 49.4 mcg/mL) were consistent with non-pregnant women's plasma concentrations in Study RA-I. Certolizumab pegol plasma concentrations were not measurable in 13 out of 15 infants at birth.

The concentration of certolizumab pegol in one infant was 0.0422 mcg/mL at birth (infant/mother plasma ratio of 0.09%). In a second infant, delivered by emergency Caesarean section, the concentration was 0.485 mcg/mL (infant/mother plasma ratio of 4.49%). At Week 4 and Week 8, all 15 infants had no measurable concentrations.

Among 16 exposed infants, one serious adverse reaction was reported in a neonate who was treated empirically with intravenous antibiotics due to an increased white blood cell count; blood cultures were negative. The certolizumab pegol plasma concentrations for this infant were not measurable at birth, Week 4, or Week 8. In another clinical study conducted in 10 pregnant women with Crohn´s disease treated with CIMZIA (400 mg every 4 weeks for every mother), certolizumab pegol concentrations were measured in maternal blood as well as in cord and infant blood at the day of birth with an assay that can measure concentrations at or above 0.41 mcg/mL.

The last dose of CIMZIA was given on average 19 days prior to delivery (range 5 to 42 days). Plasma certolizumab pegol concentrations were lower (by at least 75%) in the infants than in mothers suggesting low placental transfer of certolizumab pegol. In one infant, the plasma certolizumab pegol concentration declined from 1.02 to 0.84 mcg/mL over 4 weeks suggesting that certolizumab pegol may be eliminated at a slower rate in infants than adults.

Animal Data Because certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab' fragment (cTN3 PF) similar to certolizumab pegol. Animal reproduction studies have been performed in rats during organogenesis at intravenous doses up to 100 mg/kg (about 2.4 times the recommended human dose of 400 mg, based on the surface area) and have revealed no evidence of harm to the fetus due to cTN3 PF.

Pediatric Use The safety and effectiveness of CIMZIA for active polyarticular juvenile idiopathic arthritis has been established in pediatric patients 2 years of age and older. The use of CIMZIA in this age group is supported by evidence from adequate and well-controlled studies of CIMZIA in adults with RA, pharmacokinetic data from adults with RA and pediatric patients with JIA with active polyarthritis, and safety data from an open-label clinical study in 193 pediatric patients 2 to < 18 years of age with JIA with active polyarthritis. The observed pre-dose (trough) concentrations are generally comparable between adults with RA and pediatric patients with JIA with active polyarthritis.

The safety and effectiveness for CIMZIA in pediatric patients less than 2 years of age with pJIA have not been established. The safety and effectiveness of CIMZIA have not been established in pediatric patients for other indications. CIMZIA was evaluated for the treatment of pediatric patients with moderately to severely active Crohn's disease.

The study was ended prematurely because of a high number of patient discontinuations. Due to its inhibition of TNFα, CIMZIA administered during pregnancy could affect immune responses in the in utero -exposed newborn and infant.

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.