Certolizumab

Crohn Disease, Rheumatoid Arthritis, Psoriatic Arthritis, Plaque Psoriasis, Ankylosing Spondylitis, Spondyloarthritis

Subcutaneous Injections Crohn Disease Indicated for maintaining clinical response in patients with moderate to severe active disease who had an inadequate response to conventional therapy Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks Maintenance: 400 mg SC every 4 weeks Rheumatoid Arthritis Indicated for moderate to severe active rheumatoid arthritis (RA) Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks Psoriatic Arthritis Indicated for active psoriatic arthritis (PsA) Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks, followed by 200 mg SC every 2 weeks Maintenance: Consider 400 mg SC every 4 weeks Ankylosing Spondylitis Indicated for active ankylosing spondylitis (AS) Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks Spondyloarthritis Indicated for active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks Plaque Psoriasis Indicated for moderate-to-severe plaque psoriasis (PsO) in patients who are candidates for systemic therapy or phototherapy 400 every other week For some patients (<90 kg), consider starting at 400 mg SC (given as 2 injections of 200 mg each) initially and at Weeks 2 and 4, followed by 200 mg SC every other week

Polyarticular juvenile idiopathic arthritis Indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) <2 years Safety and efficacy not established >2 years 10 to <20 kg 100 mg SC week 0, 2, and 4 Maintenance: 50 mg SC every 2 weeks 20 to <44 kg 200 mg SC week 0, 2, and 4 Maintenance: 100 mg SC every 2 weeks >40 kg 400 mg SC week 0, 2, and 4 Maintenance: 200 mg SC every 2 weeks

SC Preparation Vials Remove from refrigerator and allow the vial(s) to sit at room temperature for 30 min before reconstituting; do not warm vial in any other way Reconstitute 200 mg vial(s) with 1 mL of sterile water for injection, using the 20-gauge needle provided; water should be directed at vial wall rather than directly to contents Gently swirl each vial for about one min without shaking, assuring that all of powder comes in contact with sterile water; avoid creating a foaming effect Continue swirling every 5 min as long as non-dissolved particles observed; full reconstitution may take as long as 30 min; final reconstituted solution contains 200 mg/mL and should be clear to opalescent, colorless to pale yellow liquid essentially free from particulates Reconstitute each 200 mg vial with 1 mL sterile water for injection, swirl to dissolve; leave vials undisturbed for up to 30 minutes to fully reconstitute Syringe Prefilled syringe contains a derivative of natural rubber latex and use caution by latex-sensitive individuals SC Administration Inject full contents of each syringe SC into separate sites on abdomen or thigh

History of hypersensitivity reaction to certolizumab pegol or to any of the excipients; reactions have included angioedema, anaphylactoid reaction, serum sickness, and urticaria

Increased risk of serious infections leading to hospitalization or death including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens (5.1). Certolizumab should be discontinued if a patient develops a serious infection or sepsis. Perform test for latent TB; if positive, start treatment for TB prior to starting Certolizumab. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which Certolizumab is a member. Certolizumab is not indicated for use in pediatric patients. Serious Infections: Certolizumab should not be initiated in patients with an active infection. Discontinue if a serious infection develops. If invasive fungal infection develops in patients who reside or travel to regions where mycoses are endemic, consider empiric antifungal therapy. Malignancies: Cases of lymphoma and other malignancies have been observed among patients receiving TNF blockers, including Certolizumab. Heart Failure: Monitor patients for new onset or worsening congestive heart failure. Hypersensitivity Reactions: Discontinue Certolizumab and institute appropriate therapy if anaphylaxis or other serious hypersensitivity reactions occur. Hepatitis B Virus Reactivation: Test for HBV infection before starting Certolizumab. If reactivation occurs, stop Certolizumab and begin anti-viral therapy Neurologic Reactions: Exacerbation or new onset demyelinating disease may occur; use caution in patients with pre-existing or recent-onset demyelinating disorders. Hematological Reactions (including leukopenia, pancytopenia and thrombocytopenia): Use with caution in patients who have ongoing, or a history of, significant hematologic abnormalities. Advise patients to seek immediate medical attention if symptoms develop; consider discontinuing Certolizumab in patients with confirmed abnormalities. Use with Anakinra, Abatacept, Ritux

Not Classi Pregnancy Pregnancy exposure registry monitors pregnancy outcomes in women exposed to the drug during pregnancy. Due to its inhibition of TNFalpha, certolizumab pegol administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant; clinical significance of low levels is unknown for in utero-exposed infants; additional data available from one exposed infant suggest that may be eliminated at a slower rate in infants than in adults Limited data from ongoing pregnancy registry on use of drug in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes Contraception Consider adequate contraception for women of childbearing potential For women planning pregnancy, consider adequate contraception for 5 months after last dose due to its elimination rate Lactation In a clinical study, minimal transfer of certolizumab pegol from plasma to breast milk was observed Percentage of maternal certolizumab pegol dose that was reaching an infant during a 24 hr period was estimated to 0.04-0.3% In addition, since certolizumab pegol is a protein that is degraded in gastrointestinal tract after oral administration, absolute bioavailability is expected to be very low in a breastfed infant; can be used during breastfeeding

An increased risk of serious infections seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit; no formal drug interaction studies were performed with rituximab or natalizumab; concomitant use of certolizumab pegol with anakinra, abatacept, rituximab, or natalizumab is not recommended Patients treated may receive vaccinations, except for live or live attenuated vaccines; no data available on response to live vaccinations or secondary transmission of infection by live vaccines in patients receiving therapy Contraindicated (14) adenovirus types 4 and 7 live, oral BCG intravesical live BCG vaccine live influenza virus vaccine quadrivalent, intranasal influenza virus vaccine trivalent, intranasal measles mumps and rubella vaccine, live measles, mumps, rubella and varicella vaccine, live rotavirus oral vaccine, live smallpox and mpox (vaccinia) vaccine, live typhoid vaccine live upadacitinib varicella virus vaccine live yellow fever vaccine zoster vaccine live

>10% URI (20%) Headache (7-18%) Nasopharyngitis (4-13%) Nausea (11%) 1-10% UTI (7%) Arthralgia (6%) Serious infections (3%) Frequency Not Defined Opportunistic infections (eg, TB) Lupus-like syndrome Malignancies Immunogenicity Hypersensitivity Blood/ lymphatic system disorder Cardiac disorder Ocular disorder Psychiatric disorder (anxiety, bipolar d/o, suicide attempt) Renal/urinary disorder Menstrual disorder Skin and subcutaneous disorder

Recombinant humanized antihuman TNF-alpha neutralizing antibody Binds to human TNFα with a KD of 90pM; TNF-alpha is a key pro-inflammatory cytokine with a central role in inflammatory processes Selectively neutralizes TNF-alpha; cross-reacts poorly with TNF from rodents and rabbits, therefore in vivo efficacy was evaluated using animal models in which human TNF-alpha was the physiologically active molecule