Certolizumab (Monograph)

Brand name: Cimzia
Drug class: Disease-modifying Antirheumatic Drugs
Molecular formula: C₂₁₁₅H₃₂₅₂N₅₅₆O₆₇₃S₁₆
CAS number: 428863-50-7

Medically reviewed by Drugs.com on Mar 19, 2024. Written by ASHP.

Introduction

Tumor necrosis factor (TNF) inhibitor and biologic disease-modifying antirheumatic drug (DMARD); a recombinant humanized Fab′ fragment of a monoclonal antibody.

Uses for Certolizumab

Crohn Disease

Used to treat moderately to severely active Crohn disease in adults who have had an inadequate response to conventional therapies.

Guidelines generally support use of TNF blocking agents for induction and maintenance therapy in adults with moderate to severe Crohn disease; however, other TNF blocking agents may be more effective than certolizumab pegol for induction of remission.

Has been used in a limited number of patients with fistulizing Crohn disease^{† [off-label]}.

Specific treatments for Crohn disease are selected according to the patient’s risk profile and disease severity.

Rheumatoid Arthritis

Used to manage moderately to severely active rheumatoid arthritis in adults. May be used alone or in combination with methotrexate or other nonbiologic DMARDs.

Disease-modifying treatments for rheumatoid arthritis include conventional DMARDs (e.g., hydroxychloroquine, leflunomide, methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, abatacept, tocilizumab, sarilumab, rituximab), and/or targeted synthetic DMARDs (e.g., Janus kinase inhibitors).

Guidelines generally support use of TNF blocking agents as add-on therapy to methotrexate in patients who do not meet treatment goals with methotrexate alone.

Specific agents for rheumatoid arthritis are selected according to current disease activity, prior therapies used, and presence of comorbidities.

Psoriatic Arthritis

Used to manage active psoriatic arthritis in adults.

Disease-modifying treatments for psoriatic arthritis include oral small molecules (OSMs; e.g., methotrexate, sulfasalazine, cyclosporine, leflunomide, apremilast), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab, ustekinumab, brodalumab, abatacept), and/or targeted synthetic DMARDs (e.g., tofacitinib).

Guidelines generally support use of TNF blocking agents as first-line treatment in patients with active psoriatic arthritis.

Ankylosing Spondylitis

Used to manage active ankylosing spondylitis in adults.

Treatments for ankylosing spondylitis include NSAIAs, conventional DMARDs (e.g., methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab), and/or targeted synthetic DMARDs (e.g., tofacitinib).

Guidelines generally support use of TNF blocking agents for treatment of ankylosing spondylitis in patients with active disease despite treatment with nonsteroidal anti-inflammatory agents (NSAIAs).

Recommendations for treatment selection in ankylosing spondylitis vary based the presence of certain comorbidities (e.g., iritis, inflammatory bowel disease).

Nonradiographic Axial Spondyloarthritis

Used to manage active nonradiographic axial spondyloarthritis in adults with objective signs of inflammation.

Treatments for nonradiographic axial spondyloarthritis include NSAIAs, conventional DMARDs (e.g., methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab), and/or targeted synthetic DMARDs (e.g., tofacitinib). Continuous NSAIA treatment is typically considered first-line for active nonradiographic axial spondyloarthritis.

Guidelines generally support use of TNF blocking agents for treatment of nonradiographic axial spondyloarthritis in patients with active disease despite treatment with NSAIAs.

Specific agents for nonradiographic axial spondyloarthritis treatment are selected according to current disease activity and prior therapies used.

Plaque Psoriasis

Used to manage moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.

Guidelines generally support use of TNF blocking agents in moderate to severe psoriasis, either as monotherapy or in combination with topical, oral, or phototherapy.

Recommendations for use and selection of psoriasis therapies vary based on patient age, disease characteristics (e.g., severity, location, presence of psoriatic arthritis), and comorbidities (e.g., inflammatory bowel disease).

Certolizumab Dosage and Administration

General

Pretreatment Screening

• Evaluate all patients for active and inactive tuberculosis prior to initiating therapy using appropriate screening tests (e.g., tuberculin skin test, chest x-ray).

• Screen all patients for hepatitis B virus (HBV) infection before initiating therapy.

• Do not initiate therapy in patients with an active infection, including clinically important localized infections.

Patient Monitoring

• Monitor closely for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock) during and after treatment; monitor for possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy.

• Perform periodic dermatologic evaluations in all patients, particularly those with risk factors for skin cancer.

• Evaluate and monitor chronic carriers of HBV during treatment and for up to several months following treatment.

Other General Considerations

• May be used alone or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs); concomitant use with biologic DMARDs, including other TNF blocking agents, is not recommended.

• Corticosteroids, nonsteroidal anti-inflammatory agents (NSAIAs), and/or other analgesics may be continued in adults with rheumatoid arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, or psoriatic arthritis.

• Administered concomitantly with aminosalicylates, corticosteroids, azathioprine, mercaptopurine, methotrexate, or anti-infective agents in patients with Crohn disease.

Administration

Sub-Q Administration

Administer by sub-Q injection into the thighs or abdomen using a 23-gauge needle. Rotate injection sites. Do not inject into areas where the skin is tender, bruised, red, or hard, or where there are scars or stretch marks.

Commercially available as a lyophilized powder that must be reconstituted (see Reconstitution under Dosage and Administration) or a prefilled syringe. Allow reconstituted solution and prefilled syringes to sit at room temperature for 30 minutes prior to administration; do not leave at room temperature for more than 2 hours.

When a 400-mg dose is required, 2 separate 200-mg doses should be administered at separate sites.

Reconstituted solution intended for use under the guidance and supervision of a clinician. Certolizumab pegol solution supplied in prefilled syringes may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training.

Reconstitution

Allow lyophilized powder kit (containing drug, diluent, syringes, needles) to sit at room temperature for 30 minutes prior to reconstitution.

Reconstitute vial containing 200 mg of certolizumab pegol lyophilized powder by adding 1 mL of sterile water for injection (provided by manufacturer) to provide a solution containing approximately 200 mg/mL. Direct sterile water for injection at vial wall rather than directly onto powder.

Gently swirl vial for about 1 minute to ensure all of the powder comes into contact with the diluent. Swirl as gently as possible to avoid foaming; do not shake. Full reconstitution may take as long as 30 minutes; swirl vial every 5 minutes as long as non-dissolved particles are observed.

Dosage

Adults

Crohn Disease

Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks (induction regimen); patients who respond may receive additional 400-mg doses every 4 weeks (maintenance regimen).

Rheumatoid Arthritis

Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks. For maintenance therapy, 400 mg every 4 weeks may be considered.

Psoriatic Arthritis

Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks. For maintenance therapy, 400 mg every 4 weeks may be considered.

Ankylosing Spondylitis

Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.

Nonradiographic Axial Spondyloarthritis

Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.

Plaque Psoriasis

Sub-Q

400 mg (as two 200-mg injections at separate sites) every 2 weeks. For some patients with body weight ≤90 kg, the following can be considered: 400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

Insufficient data available to provide dosage recommendations for patients with moderate or severe renal impairment.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Certolizumab

Contraindications

• History of hypersensitivity to certolizumab pegol or to any of the excipients.

Warnings/Precautions

Warnings

Infectious Complications

Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death. (See Boxed Warning.)

Opportunistic infections caused by bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens (e.g., aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, tuberculosis) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents (e.g., methotrexate, corticosteroids). Infections frequently are disseminated.

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept. Use of certolizumab pegol in combination with other biologic DMARDs not recommended.

Patients >65 years of age, with comorbid conditions, and/or receiving concomitant therapy with immunosuppressive agents (e.g., corticosteroids, methotrexate) may be at increased risk of infection.

Do not initiate therapy in patients with active infections, including clinically important localized infections. Consider potential risks and benefits prior to initiating therapy in patients with history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.

Closely monitor patients during and after treatment for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock), including possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy.

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient. Discontinue certolizumab pegol if serious infection or sepsis develops.

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy. When indicated, initiate appropriate antimycobacterial regimen. Consider antimycobacterial therapy prior to initiating certolizumab pegol in patients with a history of latent or active tuberculosis for whom adequate antimycobacterial treatment is unconfirmed, and in patients with a negative tuberculin skin test who have risk factors for tuberculosis. Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis. Strongly consider tuberculosis in patients who develop new infections during therapy, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.

Failure to recognize invasive fungal infections has led to delays in appropriate treatment. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic. Whenever feasible, consult specialist in fungal infections.

Malignancies and Lymphoproliferative Disorders

Cases of lymphoma and other malignancies (some fatal) reported in children, adolescents, and adults receiving TNF blocking agents; patients receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly may be at increased risk. Malignancies included lymphomas (e.g., Hodgkin disease, non-Hodgkin lymphoma, hepatosplenic T-cell lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers, leiomyosarcoma, hepatic malignancies, renal cell carcinoma). (See Boxed Warning.)

FDA has concluded that there is an increased risk of malignancy with TNF blocking agents; however, the strength of the association is not fully characterized.

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.

Carefully consider risks and benefits of TNF blocking agents, especially in adolescents and young adults and especially in the treatment of Crohn disease or ulcerative colitis.

Periodic dermatologic evaluations recommended for all patients, particularly those with risk factors for skin cancer.

Other Warnings/Precautions

Cardiovascular Effects

Worsening CHF and new-onset CHF reported in patients receiving TNF blocking agents; not studied in patients with CHF.

If used in patients with CHF, caution and careful monitoring recommended.

Sensitivity Reactions

Angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria reported rarely, sometimes after the first dose.

If allergic reaction occurs, discontinue certolizumab pegol and initiate appropriate treatment. Use caution if administering certolizumab pegol to patients who have experienced a severe hypersensitivity reaction to another TNF blocking agent.

Needle shield inside the removable cap of the certolizumab pegol prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in latex-sensitive patients.

HBV Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of this virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]). Fatalities reported. Use of multiple immunosuppressive agents may contribute to HBV reactivation.

Screen all patients for HBV infection prior to initiation of therapy. Consultation with an HBV infection specialist is recommended for those who test positive.

Evaluate and monitor HBV carriers before, during, and for up to several months after therapy. Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established. Discontinue certolizumab pegol and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs. Not known whether certolizumab pegol can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.

Nervous System Effects

New onset or exacerbation of central or peripheral nervous system demyelinating disorders (e.g., multiple sclerosis, Guillain-Barré syndrome) reported rarely. Exercise caution when considering certolizumab pegol therapy in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

Seizure disorder, optic neuritis, and peripheral neuropathy reported rarely.

Hematologic Effects

Pancytopenia (including aplastic anemia), leukopenia, and thrombocytopenia reported rarely; causal relationship unclear.

Use with caution in patients with a history of substantial hematologic abnormalities. Consider discontinuing therapy if substantial hematologic abnormalities occur.

Immunologic Reactions and Antibody Formation

Possible formation of autoimmune antibodies. Lupus-like syndrome reported rarely. Discontinue therapy if manifestations suggestive of a lupus-like syndrome occur.

Antibodies to certolizumab pegol may develop. Incidence of antibody formation lower in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate).

Antibody formation associated with lower plasma drug concentrations and reduced efficacy in patients with rheumatoid arthritis and psoriasis. In patients with nonradiographic axial spondyloarthritis, higher antibody titers associated with lower plasma drug concentrations. In patients with Crohn disease, antibody formation associated with lower plasma drug concentrations, but no apparent association between antibody development and efficacy or adverse events.

Immunization

Avoid live vaccines.

Immunosuppression

Safety and efficacy in immunosuppressed patients not evaluated.

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including certolizumab pegol. Most patients experienced improvement following discontinuance of the TNF blocking agent. A change to a different subtype of plaque psoriasis (e.g., erythrodermic, pustular, guttate) rarely observed.

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.

Specific Populations

Pregnancy

Limited data from an ongoing pregnancy registry insufficient to inform a risk of major birth defects or other adverse pregnancy outcomes. However, studies indicate that placental transfer of certolizumab pegol is negligible to low. No adverse developmental effects observed in animal reproduction studies.

Data suggest increased disease activity in women with rheumatoid arthritis or inflammatory bowel disease is associated with increased risk of adverse pregnancy outcomes (e.g., fetal loss, preterm delivery, low birth weight, small size for gestational age at birth).

In utero exposure to certolizumab pegol may affect immune responses of newborns and infants.

Limited data suggest that certolizumab pegol may be eliminated at a slower rate in infants than in adults.

Consider risks and benefits of administering live vaccines to infants exposed to the drug in utero; safety of live vaccines in such infants is unknown.

Pregnancy registry at 877-311-8972 or [Web]/pregnancy-studies.

Lactation

Distributes into human breast milk. No serious adverse reactions reported and not detected in plasma of breast-fed infants. No data on effects on milk production.

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for certolizumab pegol and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Malignancies, some fatal, reported in children and adolescents who received TNF-blocking agents.

Neonates and infants exposed to certolizumab pegol in utero may have impaired immune responses. Certolizumab pegol concentrations were negligible in most infants exposed to the drug in utero; clinical importance is unknown. The drug may be eliminated more slowly in infants than in adults. Consider risks and benefits of administering live vaccines to infants exposed to certolizumab pegol in utero; safety of live vaccines in these infants is unknown.

Geriatric Use

No substantial differences in response relative to younger adults.

Possible increased incidence of infections in geriatric patients; use with caution.

Common Adverse Effects

Common adverse effects (7%) include upper respiratory tract infection, rash, and urinary tract infection.

Drug Interactions

No formal drug interaction studies with oral corticosteroids, NSAIAs, analgesics, or immunosuppressants to date.

Has been used concomitantly with corticosteroids, NSAIAs, and/or other analgesics in clinical studies; however, formal drug interaction studies with these agents not performed to date. Also has been used concomitantly with aminosalicylates, azathioprine, mercaptopurine, methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs), and/or anti-infective agents.

Biologic Antirheumatic Agents

Concomitant use of certolizumab pegol and other biologic DMARDs not recommended.

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase the risk of infection.

Vaccines

Avoid live vaccines. No data available on secondary transmission of infection by live vaccines in certolizumab pegol-treated patients.

Specific Drugs and Laboratory Tests

Certolizumab Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 80% following sub-Q administration. Peak serum concentrations achieved in 54–171 hours.

Distribution

Extent

Crosses the placenta in small amounts.

Elimination

Metabolism

Not studied.

Elimination Route

Not studied. Polyethylene glycol moiety excreted principally in urine.

Half-life

Approximately 14 days.

Special Populations

Pharmacokinetics of certolizumab pegol not formally studied in patients with renal impairment. However, pharmacokinetics of polyethylene glycol moiety dependent on renal function.

Among adults, age does not appear to influence pharmacokinetics.

Clearance of certolizumab pegol is higher with increasing body weight; however, no clinically important weight-related differences observed.

In patients with certolizumab pegol antibodies, clearance of certolizumab is higher.

No gender-related pharmacokinetic differences apparent.

Stability

Storage

Sub-Q

Injection in Prefilled Syringes

2–8°C. Do not freeze. Protect from light; store in original carton until administration.

Powder for Injection

2–8°C. Do not freeze. Protect from light; store in original carton until administration.

May store reconstituted solution for up to 24 hours at 2–8°C. Do not freeze.

Actions

• Recombinant humanized Fab′ fragment of an anti-TNF monoclonal antibody conjugated to an approximately 40-kilodalton polyethylene glycol (PEG2MAL40K) in order to prolong the half-life.

• Binds with high affinity to TNF-α, a cytokine involved in the regulation of immune response.

• Does not contain a fragment crystallizable (Fc) region or induce complement activation, antibody-dependent cellular cytotoxicity, apoptosis, or neutrophil degranulation in vitro.

Advice to Patients

• Importance of advising patients about potential benefits and risks of certolizumab pegol. Importance of patients reading the manufacturer’s patient information (medication guide) prior to initiation of therapy and before each injection of the drug.

• Importance of instructing patient and/or caregiver regarding proper dosage and administration of certolizumab pegol, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.

• Increased susceptibility to infection. Importance of informing clinicians promptly if any signs or symptoms suggestive of infection (e.g., persistent fever, sweating, cough, dyspnea, fatigue) occur. Importance of informing health care providers about any ongoing active infections.

• Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, and other malignancies with use of TNF blocking agents. Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease. Importance of promptly informing clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; hepatomegaly or splenomegaly) occur.

• Importance of informing clinician of any new or worsening medical conditions (e.g., heart failure, neurologic disease [e.g., demyelinating disorders], autoimmune disorders [e.g., lupus-like syndrome], cytopenias, psoriasis).

• Importance of informing latex-sensitive patients that the needle shield inside the removable cap of the certolizumab pegol prefilled syringe contains a derivative of natural rubber latex.

• Importance of promptly contacting a clinician if manifestations of an allergic reaction (e.g., urticaria, facial swelling, difficulty breathing) occur.

• Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurrent infections.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

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