Version July 2025
Patients treated with certolizumab are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.
Certolizumab should be discontinued if a patient develops a serious infection or sepsis.
Reported infections include the following:
Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before certolizumab use and during therapy. Treatment for latent infections should be initiated prior to certolizumab 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 antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria.
The risks and benefits of treatment with certolizumab 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 certolizumab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers.
Dosage guidance:
Dosage form information: The appropriate dosage form is dependent on the dose: Doses <200 mg can only be prepared from the vial and administered by a health care professional; a prefilled syringe may be used for doses ≥200 mg and can be self-administered or the dose can be prepared from the vial and administered by a health care professional.
Juvenile idiopathic arthritis (JIA), polyarticular:
Children ≥2 years and Adolescents:
10 to <20 kg:
Loading dose: Vials: SUBQ: 100 mg at weeks 0, 2, and 4.
Maintenance dose: Vials: SUBQ: 50 mg every 2 weeks.
20 kg to <40 kg:
Loading dose: Prefilled syringe, vials: SUBQ: 200 mg at weeks 0, 2, and 4.
Maintenance dose: Vials: SUBQ: 100 mg every 2 weeks.
≥40 kg:
Loading dose: Prefilled syringes, vials: SUBQ: 400 mg (administered as two 200 mg injections) at weeks 0, 2, and 4.
Maintenance dose: Prefilled syringe, vials: SUBQ: 200 mg every 2 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); pharmacokinetics of the pegylated (polyethylene glycol) component of certolizumab are expected to be dependent on kidney function.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Certolizumab pegol: Drug information")
Dosage guidance:
Safety: Prior to initiation, certain assessments (clinical and laboratory) are required with documentation and age-appropriate vaccinations should be up to date. In general, live vaccines should not be administered within 4 weeks prior to starting therapy (Ref). Refer to institutional protocols for vaccination and monitoring requirements prior to initiating therapy.
Dosing: Each 400 mg dose should be administered as 2 injections of 200 mg each.
Ankylosing spondylitis: SUBQ: Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 200 mg every 2 weeks or 400 mg every 4 weeks.
Axial spondyloarthritis, nonradiographic: SUBQ: Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 200 mg every 2 weeks or 400 mg every 4 weeks.
Crohn disease (alternative agent): SUBQ: Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 400 mg every 4 weeks (Ref).
Plaque psoriasis: SUBQ: 400 mg every other week. Note: For patients ≤90 kg, an initial dose of 400 mg at weeks 0, 2, and 4 followed by 200 mg every other week thereafter may be considered.
Psoriatic arthritis: SUBQ: Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 200 mg every other week. May consider maintenance dose of 400 mg every 4 weeks.
Rheumatoid arthritis:
Note: For use as an alternative to methotrexate in disease-modifying antirheumatic drug–naive patients with moderate to high disease activity, or as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy (Ref).
SUBQ: Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 200 mg every other week. May consider maintenance dose of 400 mg every 4 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); pharmacokinetics of the pegylated (polyethylene glycol) component of certolizumab is expected to be dependent on renal function.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Gastrointestinal: Nausea (≤11% [Schreiber 2005])
Hematologic & oncologic: Positive ANA titer (children, adolescents: 17%; adults: 4%)
Immunologic: Antibody development (children, adolescents: 92%; adults: 7% to 23% [neutralizing: 3% to 8%])
Infection: Infection (38%; serious infection [children, adolescents: 13%; adults: 3%])
Respiratory: Upper respiratory tract infection (18% to 22%)
1% to 10%:
Dermatologic: Skin rash (9%)
Genitourinary: Urinary tract infection (7% to 8%)
Hepatic: Increased liver enzymes (≤4%)
Infection: Herpes virus infection (2%)
Local: Injection-site reaction (2% to 3%; including bruising at injection site, erythema at injection site, pain at injection site, skin discoloration at injection site, swelling at injection site)
Nervous system: Headache (4%)
Neuromuscular & skeletal: Arthralgia (6%)
Respiratory: Cough (3%)
<1%:
Hematologic & oncologic: Hodgkin lymphoma, malignant lymphoma
Neuromuscular & skeletal: Lupus-like syndrome
Frequency not defined:
Dermatologic: Cellulitis, urticaria
Gastrointestinal: Diarrhea, gastroenteritis, intestinal obstruction
Hematologic & oncologic: Hematoma
Infection: Abscess (abdominal), aspergillosis, bacterial infection, blastomycosis, candidiasis, coccidioidomycosis, fungal infection, histoplasmosis, listeriosis, opportunistic infection, reactivation of HBV, sepsis, viral infection
Renal: Pyelonephritis
Respiratory: Infection due to an organism in genus Pneumocystis, lower respiratory tract infection, pneumonia, tuberculosis (including reactivated tuberculosis)
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Heart failure, peripheral edema
Dermatologic: Erythema nodosum, malignant melanoma, Merkel cell carcinoma
Gastrointestinal: Abdominal pain
Hematologic & oncologic: Cytopenia (including leukopenia, pancytopenia, thrombocytopenia), hepatosplenic T-cell lymphomas, malignant neoplasm
Hepatic: Autoimmune hepatitis (Shelton 2015), hepatotoxicity (idiosyncratic) (Chalasani 2021)
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema), serum sickness
Immunologic: Sarcoidosis
Nervous system: Peripheral neuropathy, seizure
Neuromuscular & skeletal: Limb pain
Ophthalmic: Optic neuritis
Hypersensitivity to certolizumab pegol or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Tuberculosis (TB) disease (active TB) or other severe infections (eg, sepsis, abscesses, opportunistic infections); moderate to severe heart failure (NYHA Class III/IV)
Concerns related to adverse effects:
• Antibody formation: Formation of neutralizing anti-drug antibodies may occur with biologic tumor necrosis factor (TNF) inhibitors and may be associated with loss of efficacy (AAD-NPF [Menter 2019]).
• Autoimmune disorder: Autoantibody formation may develop; rarely resulting in autoimmune disorder, including lupus-like syndrome; monitor and discontinue if symptoms develop.
• Demyelinating CNS disease: Rare cases of optic neuritis, seizure, peripheral neuropathy, and demyelinating disease (eg, multiple sclerosis, Guillain-Barré syndrome; new onset or exacerbation) have been reported. Use with caution in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.
• Hematologic effects: Rare cases of pancytopenia and other significant cytopenias, including aplastic anemia, have been reported with TNF-blocking agents. Leukopenia and thrombocytopenia have occurred with certolizumab. Consider discontinuing therapy with significant hematologic abnormalities. Use with caution in patients with underlying hematologic disorders.
• Hepatitis B: Rare reactivation of hepatitis B virus (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Patients who test positive for HBV surface antigen should be referred for hepatitis B evaluation/treatment prior to certolizumab initiation. Monitor for clinical and laboratory signs of active infection during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.
• Hypersensitivity: Hypersensitivity reactions, including angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness and urticaria have been reported (rarely) with treatment. Some of these reactions have occurred after the first dose. Discontinue and do not resume therapy if hypersensitivity occurs. Use with caution in patients who have experienced hypersensitivity with other TNF blockers.
• Immunogenicity: Development of antibodies to certolizumab during therapy may occur. Antibody-positive patients may have an increased incidence of adverse events (including injection site pain/erythema, abdominal pain, and erythema nodosum) and may have lower certolizumab concentrations with reduced efficacy.
• Infections: [US Boxed Warning]: Patients treated with certolizumab are at increased risk for developing serious infections, which may result in hospitalization or death; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate, corticosteroids) and may present as disseminated (rather than local) disease. Tuberculosis (TB) disease (active TB) (including reactivation of TB infection [latent TB]), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral, or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving certolizumab. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks vs benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. The elderly, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at a greater risk of infection. Consider risks vs benefits prior to initiating therapy in patients with a history of opportunistic infection; patients who have resided or traveled in areas of endemic TB or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; and patients with underlying conditions, which may predispose them to infection. Do not initiate certolizumab therapy with active infection, including clinically important localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely.
• Malignancy: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescent patients receiving TNF-blocking agents. Approximately half of the malignancies reported in children were lymphomas (Hodgkin and non-Hodgkin) while other cases varied and included malignancies not typically observed in this population. The onset of malignancy was after a median of 30 months (range: 1 to 84 months) after the initiation of the TNF-blocking agent. Use of TNF blockers may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. Chronic immunosuppressant therapy use may be a predisposing factor for malignancy development; rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been associated with TNF-blocking agents, including certolizumab, primarily reported in adolescent and young adult males with Crohn disease or ulcerative colitis, most of whom had received concurrent treatment with azathioprine and/or 6-mercaptopurine. Melanoma and Merkel cell carcinoma have been reported with TNF-blocking agents including certolizumab. Perform periodic skin examinations in all patients during therapy, particularly those at increased risk for skin cancer.
• Tuberculosis: [US Boxed Warning]: Tuberculosis (TB) (disseminated or extrapulmonary disease) has been reported; both reactivation of TB infection (latent TB) and new infections have been reported. Patients should be tested for TB infection before and during therapy; consider treatment of TB infection prior to certolizumab treatment. Monitor for development of TB during and after treatment, including patients with initial negative skin tests. Use with caution in patients who have resided in regions where TB is endemic. Consider antituberculosis treatment prior to initiation of certolizumab in patients with a history of TB infection or disease (active TB) if adequate treatment course cannot be confirmed, and for patients with risk factors for tuberculosis despite a negative test. Strongly consider TB in patients who develop a new infection during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of TB, or who have had close contact with a person with TB disease.
Disease-related concerns:
• Heart failure: Use with caution in heart failure patients; worsening heart failure and new-onset heart failure have been reported with TNF blockers, including certolizumab; monitor closely. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
• HIV: Use with caution in HIV-positive patients; TNF-α inhibitors may be appropriate in patients receiving highly active antiretroviral therapy, provided they have normal CD4 counts, no viral load, and no recent opportunistic infections (AAD-NPF [Menter 2019]).
• Renal impairment: Use has not been studied in patients with renal impairment; however, the pharmacokinetics of the pegylated (polyethylene glycol) component may be dependent on renal function.
Special populations:
• Older adult: Use with caution in elderly patients, may be at higher risk for infections.
• Patients with rheumatic musculoskeletal disease undergoing hip or knee replacement surgery: Hold biologic disease-modifying antirheumatic drugs (DMARDs) prior to surgery and plan surgery after the next dose is due. Surgery can occur after holding medication for 1 full dosing cycle (eg, for medications administered every 4 weeks, schedule surgery 5 weeks from last administered dose); therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk). Decisions to withhold therapy should be based on shared decision making; ensure the patient and their provider weigh risks of interrupting therapy and disease control versus risks of continuing therapy and surgical complications (ACR/AAHKS [Goodman 2022]).
• Pediatric: Malignancies have been reported among children and adolescents receiving TNF-blocking agents.
Dosage form specific:
• Latex: The packaging (needle shield inside the removable cap of prefilled syringe) may contain a plastic derived from natural rubber latex.
Other warnings/precautions:
• Immunizations: Patients should be up to date with all immunizations before initiating therapy; avoid use of live vaccines during or immediately prior to therapy initiation.
Although certolizumab pegol is indicated for moderate to severe Crohn disease in adults, safety and efficacy were not shown in pediatric patients 6 to 17 years of age (n=99) in a multiple dose, open-label, randomized, parallel-group trial; the trial closed early due to a high number subjects discontinuing the study.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Subcutaneous, Powder for reconstitution [preservative free]:
Cimzia: 200 mg
Prefilled Syringe Kit, Subcutaneous [preservative free]:
Cimzia (2 Syringe): 200 mg/mL (1 ea)
Cimzia-Starter: 6 X 200 mg/mL (1 ea)
No
Kit (Cimzia Subcutaneous)
2 X 200 mg (per each): $7,199.32
Prefilled Syringe Kit (Cimzia (2 Syringe) Subcutaneous)
200 mg/mL (per each): $7,199.32
Prefilled Syringe Kit (Cimzia-Starter Subcutaneous)
200 mg/mL (per each): $7,199.32
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Auto-injector Kit, Subcutaneous:
Cimzia (2 Pen): 200 mg/mL (1 ea)
Prefilled Syringe Kit, Subcutaneous:
Cimzia (2 Syringe): 2 x 200 mg/mL (1 ea)
SUBQ: Administer subcutaneously into the thigh or abdomen (avoiding areas within 2 inches of navel). For a 400 mg (2 syringes) dose, administer each 200 mg syringe at a separate site; rotate injection sites (at least 1 inch from the previous site). Do not administer to areas where skin is tender, bruised, red, hard, or has scars or stretch marks.
Syringes prepared from vials: Must be administered by a health care professional; appropriate for all doses. Prior to use, attach 23-gauge needle. Gently pinch skin at injection site, insert needle; slowly and steadily push plunger rod until it completely stops and the syringe is empty.
Prefilled syringes: Only for ≥200 mg dose; may be administered by patients or caregivers after training. Gently pinch skin at injection site, insert needle at a 45-degree angle; slowly and steadily push plunger rod until it completely stops and the syringe is empty.
SUBQ: Bring to room temperature prior to administration. After reconstitution (of vials), draw each vial into separate syringes (using 20-gauge needles).
Administer subcutaneously (using provided 23-gauge needle) into the thigh or abdomen (avoiding areas within 2 inches of navel). For a 400 mg (2 syringes) dose, administer each 200 mg syringe at a separate site; rotate injection sites (at least 1 inch from the previous site). Do not administer to areas where skin is tender, bruised, red, hard, or has scars or stretch marks.
Prefilled syringes may be self-administered after proper training.
Store intact vials and syringes at 2°C to 8°C (36°F to 46°F); do not freeze. Do not separate contents of carton prior to use. Protect from light. Bring to room temperature prior to administration. Prefilled syringes may be stored at ≤25°C (≤77°F) for ≤7 days; write date removed from refrigerator and discard if not used within 7 days. Store in original carton (to protect from light) and do not return to refrigerator.
Store reconstituted solution for up to 24 hours at 2°C to 8°C (36°F to 46°F) (do not freeze); however, do not leave at room temperature for more than 2 hours prior to administration. Discard unused portion of vial or syringe.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125160s275lbl.pdf#page=42, must be dispensed with this medication.
Treatment of active polyarticular juvenile idiopathic arthritis (FDA approved in pediatric patients ≥2 years of age); treatment of active ankylosing spondylitis (FDA approved in adults); treatment of nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation (FDA approved in adults); treatment of moderately to severely active Crohn disease in patients who have inadequate response to conventional therapy (FDA approved in adults); treatment of moderate to severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy (FDA approved in adults); treatment of active psoriatic arthritis (FDA approved in adults); treatment of moderately to severely active rheumatoid arthritis as monotherapy or in combination with nonbiological disease-modifying antirheumatic drugs (FDA approved in adults).
Certolizumab pegol may be confused with sarilumab.
Cimzia may be confused with Cyramza
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abatacept: Anti-TNF Agents may increase immunosuppressive effects of Abatacept. Risk X: Avoid
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Anakinra: Anti-TNF Agents may increase adverse/toxic effects of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs may increase immunosuppressive effects of Anifrolumab. Risk X: Avoid
Anti-TNF Agents: May increase immunosuppressive effects of Certolizumab Pegol. Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Belimumab: May increase immunosuppressive effects of Biologic Disease-Modifying Antirheumatic Drugs. Management: Consider alternatives to the use of belimumab with other biologic therapies. Monitor closely for increased toxicities related to additive immunosuppression (ie, infection, malignancy) if combined. Risk D: Consider Therapy Modification
Biologic Disease-Modifying Antirheumatic Drugs: May increase immunosuppressive effects of Biologic Disease-Modifying Antirheumatic Drugs. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Canakinumab: Anti-TNF Agents may increase adverse/toxic effects of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pegloticase: May decrease therapeutic effects of PEGylated Drug Products. Risk C: Monitor
Pegvaliase: PEGylated Drug Products may increase adverse/toxic effects of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Rilonacept: Anti-TNF Agents may increase adverse/toxic effects of Rilonacept. Risk X: Avoid
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Thiopurine Analogs: Anti-TNF Agents may increase adverse/toxic effects of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider Therapy Modification
Vedolizumab: Anti-TNF Agents may increase adverse/toxic effects of Vedolizumab. Risk X: Avoid
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
The American Academy of Dermatology considers tumor necrosis factor alpha (TNFα) blocking agents for the treatment of psoriasis to be compatible for use in patients planning to father a child (AAD-NPF [Menter 2019]). Patients with psoriasis planning to become pregnant may continue treatment with certolizumab pegol. Patients with well-controlled psoriasis who wish to avoid fetal exposure can consider discontinuing certolizumab pegol 10 weeks prior to attempting to conceive (Rademaker 2018).
Inflammatory bowel disease is associated with adverse pregnancy outcomes; maternal disease and serum levels of biologic therapy should be optimized prior to conception. Biologics, such as certolizumab, may be continued in patients with inflammatory bowel disease planning to become pregnant (Mahadevan 2019). Treatment algorithms are available for use of biologics in patients with Crohn disease who are planning to become pregnant (Weizman 2019).
Placental transfer of certolizumab pegol is minimal (Förger 2016; Mariette 2018).
Certolizumab pegol is a humanized Fab-fragment conjugated to polyethylene glycol (PEG). Placental transfer of Fab-fragments is expected to be low to absent (Pentsuk 2009).
Serum concentrations of certolizumab pegol in 12 infants of 10 mothers were ≥75% lower than the maternal serum at delivery (last maternal dose of 400 mg given 5 to 42 days prior to birth; median: 19 days). PEG was not present in infant plasma or cord blood. Although placental transfer of certolizumab pegol was low, based on the rate certolizumab pegol decline in one case, infants may have a slower rate of elimination than adults (Mahadevan 2013). In a study with information from 11 infants, certolizumab pegol cord concentrations were below the limit of detection (n=8) to 1 mcg/mL (n=3). In comparison, median maternal serum levels were 32.97 mcg/mL following administration of certolizumab 200 mg every 2 weeks (Förger 2016). Information is also available from a multicenter study which included 16 mothers on various certolizumab doses during pregnancy. All mothers in the study had therapeutic drug concentrations. The median time between the last maternal dose and delivery was 11 days (range: 1 to 27 days). Certolizumab pegol was measurable in the cord blood in one of 14 infants; concentrations were 0.09% of the maternal plasma levels. Certolizumab pegol was not present in infant serum 4 and 8 weeks after birth. In addition, 14 of 15 umbilical cord samples did not have detectable concentrations of PEG (Mariette 2018).
Pregnancy outcome data from the UCB Pharma safety database collected through March 6, 2017 has been published. Among 528 prospective pregnancies with 538 known outcomes (10 twin pregnancies), 85.3% resulted in live births; among these, 81.2% had at least first trimester exposure. Other outcomes reported were miscarriage (8.7%), elective abortions (5%), major congenital malformations (1.7%), and stillbirths (0.9%). There were no patterns of birth defects among the eight infants with congenital malformations and the rate of birth defects was not greater than that observed in the general population. Pregnancy outcomes were not known for 411 cases reported to the database; 198 additional pregnancies were ongoing at the time of the report (Clowse 2018). Information related to this class of medications is emerging, but based on available data, tumor necrosis factor alpha (TNFα) blocking agents are considered to have low to moderate risk when used in pregnancy (ACOG 776 2019).
Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).
Use of immune modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 776 2019). The American Academy of Dermatology considers TNFα blocking agents for the treatment of psoriasis to be compatible with pregnancy (AAD-NPF [Menter 2019]). When treatment for inflammatory bowel disease is needed in pregnant patients, certolizumab pegol can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer (Mahadevan 2019).
Data collection to monitor pregnancy and infant outcomes following exposure to certolizumab pegol is ongoing. Health care providers are encouraged to enroll women exposed to certolizumab pegol during pregnancy in the MotherToBaby Pregnancy Studies by contacting the Organization of Teratology Information Specialists (OTIS) (877-311-8972) or http://mothertobaby.org/pregnancy-studies/.
Monitor improvement of symptoms and physical function assessments. Latent TB screening prior to initiating and during therapy; signs/symptoms of infection (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) including periodic skin examinations.
Certolizumab is a pegylated humanized antibody Fab’ fragment of tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Certolizumab binds to and selectively neutralizes human TNF-alpha activity. Elevated levels of TNF-alpha have a role in the inflammatory process associated with Crohn disease and in joint destruction associated with rheumatoid arthritis. Since it is not a complete antibody (lacks Fc region), it does not induce complement activation, antibody-dependent cell-mediated cytotoxicity, or apoptosis. Pegylation of certolizumab allows for delayed elimination and therefore an extended half-life.
Onset of action: Psoriasis: Response best determined after 3 to 4 months (AAD-NPF [Menter 2019]).
Distribution: Vss: 4.7 to 8 L.
Bioavailability: SubQ: ~80% (range: 76% to 88%).
Half-life elimination: ~14 days.
Time to peak, plasma: 54 to 171 hours.
Body weight: Pharmacokinetic exposure is inversely related to body weight; however, no therapeutic benefit is expected from a weight-adjusted dose regimen.
