Certolizumab (Cimzia) is a humanized monoclonal antibody “Fab fragment” that binds to and neutralizes the activity of TNF alpha activity. Since it lacks the Fc region, it does not activate the complement system, induce apoptosis, or mediate antibody-dependent cell cytotoxicity. Neutralizing the TNF activity results in inhibition of the inflammatory processes as seen in Crohn's disease and moderately severe Rheumatoid arthritis.

Certolizumab (Cimzia) Uses:

Certolizumab is indicated in the following conditions:

1. Adult patients with ankylosing spondylitis
2. Moderate to severely active Crohn's colitis not responding to conventional therapy
3. Moderate to severe plaque psoriasis who require systemic therapy or are candidates for phototherapy.
4. Adult patients with active psoriatic arthritis
5. Adult patients with moderate to severely active Rheumatoid arthritis as monotherapy or in combination with conventional DMARDs.

Contraindications to Certolizumab (Cimzia):

• Hypersensitivity to certolizumab and any of its components
• Patients with active tuberculosis and any other severe infections such as abscesses, sepsis, or opportunistic infections.
• This drug should not be recommended to patients suffering from moderate or severe heart disease (NYHA III and IV).

Certolizumab - Warnings and precautions:

• Immunogenicity:
  • Some patients may develop autoantibodies, which can lead to lupus-like symptoms. The signs and symptoms should be recognized so that the drug can be stopped.
• Demyelinating diseases:
  • Patients with a history of demyelinating diseases should not use it.
  • It has been associated with demyelinating conditions such as multiple sclerosis and optic neuritis.
• Blood disorders:
  • Patients with underlying hematological conditions like anemia or thrombocytopenia should not use it.
  • It has been associated with severe cytopenias, including Aplastic Anemia.
  • If you are diagnosed with serious hematological conditions, the drug should be stopped immediately.
• Hepatitis B infection:
  • Patients who have been chronically ill with hepatitis B may be reactivated.
  • Before initiating treatment, patients should be examined.
  • Patients with a positive HBsAg must be treated before the therapy.
  • Reactivation should not occur during treatment. Instead, appropriate antiviral therapy should begin.
• Allergy reactions:
  • Hypotension, angioedema and rash may be signs of allergic reactions.
  • These patients should be stopped from receiving therapy and treated accordingly.
• Formation of antibodies:
  • Patients may develop antibodies against certolizumab.
  • Patients may experience increased sensitivity and pain at the injection site. Certolizumab levels are also decreased in these patients, which can lead to lower efficacy.
• Infections
  • Patients are at high risk for reactivation and invasive bacterial infection, which can lead to hospitalizations or even death.
  • Concomitant use of conventional DMARDs like methotrexate and steroids might increase the risk of infections further.
  • Reports of invasive fungal infections such as blastomycosis and candidiasis, histoplasmosis and histoplasmosis have been made.
  • Others infections, including bacterial, viral and opportunistic ones like legionellosis or listeriosis, have also been reported.
  • If there is any indication of infection, it is best to stop all therapy.
  • Patients at high risk for fungal infections may need to be treated with empiric antifungal therapy.
  • Patients with endemic diseases, elderly patients and those taking immunosuppressants should weigh the benefits and risks.
  • Before initiating treatment with a tuberculin-gamma release assay or tuberculin skin test, patients should be tested.
• Cancers
  • Certolizumab was also associated with an increase in malignancies such as lymphoma.
  • These malignancies can also be increased by the use of immunosuppressants and autoimmune rheumatic disease.
  • These complications are more common in children and adults who have used certolizumab over a long period of time (mean duration: 30 months).
  • It has been associated with Lymphomas (both Hodgkin’s and non-Hodgkins), Hepatosplenic T Cell Lympoma (a rare form of T cell lymphoma), Melanoma, and Merkel cell carcinoma.
  • To detect skin neoplasms early, periodic skin examination is important.
• Cardiovascular disease
  • Certolizumab can also cause myocardial toxicities and may worsen underlying myocardial dysfunction.
  • Heart failure should be monitored in all patients, especially those who are elderly or have a history of heart disease.
• Kidney disease
  • Patients suffering from renal impairment should be cautious about taking the drug.
• Drug interactions:
  • It is important to monitor patients for drug-drug interactions.
• Vaccination:
  • Before starting treatment with certolizumab, patients should be immunized.

Certolizumab (Cimzia) Dose in Adults

NOTE: Each 400 mg dose should be administered as two injections of 200 mg each.

• Ankylosing spondylitis:
  • Initial dose: 400 mg subcutaneously, repeated at 2 and 4 weeks
  • Maintenance dose: 200 mg every 2 weeks or 400 mg every 4 weekly subcutaneously

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  Certolizumab (Cimzia) dose in Crohn’s disease:

  • Initial dose: 400 mg subcutaneously, repeated at 2 and 4 weeks
  • Maintenance dose: 400 mg every 4 weekly subcutaneously

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  Certolizumab (Cimzia) dosein Plaque Psoriasis:

  • Initial dose: 400 mg subcutaneously every other week.
  • Patients weighing less than 90 kgs: 400 mg s/c at 0, 2 and 4 weeks followed by 200 mg every other week may be considered.

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  Certolizumab (Cimzia) dose in Psoriatic arthritis:

  • Initial dose: 400 mg subcutaneously, repeated at 2 and 4 weeks
  • Maintenance dose: 200 mg every 2 weeks or 400 mg every 4 weekly subcutaneously

• Certolizumab Dose in Rheumatoid arthritis:

  • Initial dose: 400 mg subcutaneously, repeated at 2 and 4 weeks
  • Maintenance dose: 200 mg every 2 weeks or 400 mg every 4 weekly subcutaneously
  • May be used as monotherapy or in combination with other DMARDs

Certolizumab (Cimzia) Dose in Childrens

Not recommended for use in children

Certolizumab (Cimzia) Dose in Renal Disease:

The manufacturer has not advised any dose adjustment in patients with impaired renal functions, however, because of the pegylated component, it should be used with caution in these patients

Certolizumab (Cimzia) Dose in Liver Disease:

• The manufacturer has not advised any dose adjustment in patients with hepatic impairment.
• Certolizumab induced liver injury is not known, however, the reactivation of hepatitis B and a theoretical risk of autoimmune hepatitis is there.

How to administer Certolizumab (Cimzia)?

• Bring the vial to room temperature before administering it. Reconstitute each vial into a 20 gauge-needle syringe.
• Administer subcutaneously using a 23 gauge needle into the thigh or abdomen.
• Do not inject into an inflamed or bruised site. Rotate the site of injections.
• The 400 mg dose should be divided and injected into two separate sites.
• Prefilled syringes can be administered by the patient at home after proper training.

Pregnancy Risk Category B

• Certolizumab crosses the placenta, therapy should, therefore, be withheld after 30 weeks of gestation.
• Certolizumab serum levels were 75% lower in mothers than those of the mothers in one study. 
• It is safer than other Biological DMARDs and can be used during pregnancy.

Certolizumab is considered compatible with breastfeeding. 

• The physician must consider the health of the baby, as well as the benefits to the mother.

Side effects of Certolizumab (Cimzia):

• Nausea,
• antibody formation,
• infections especially upper respiratory tract infections and serious bacterial/ opportunistic infections.

Less common side effects:

• Cardiovascular effects: hypertension, angina pectoris, atrial fibrillation, cardiac arrhythmias, cardiac failure, hypertensive heart diseases, ischemic heart diseases, myocardial infarction, pericarditis, pericardial effusion, transient ischemic attacks, and cerebrovascular events.
• CNS side effects: headache, anxiety, bipolar mood disorders, fatigue, and suicidal ideation
• Skin-related side effects: rash, alopecia, dermatitis, urticaria and erythema nodosum
• Genitourinary and endocrine disorders: menstrual irregularities, urinary tract infections, and nephrotic syndrome.
• Blood-related side effects: anemia, leukopenia, pancytopenia, lymphadenopathy, thrombophlebitis, hemorrhage, and hypercoagulable states
• Liver-related side effects: hepatitis and transaminitis
• Neuromuscular side effects: arthralgias and back pain
• Ophthalmic: optic neuritis, retinal hemorrhages, and uveitis
• Renal: renal failure
• Respiratory: cough, nasopharyngitis, tuberculosis, and bronchitis
• Miscellaneous: Fever

Rare side effects:

• Abdominal pain,
• aplastic anemia,
• demyelinating diseases,
• diarrhea,
• fistula,
• hepatosplenic T-cell lymphoma,
• herpes virus infection,
• hypersensitivity reactions,
• injection site reactions,
• intestinal obstruction,
• leukemia,
• lupus-like syndrome,
• lymphoma,
• malignant neoplasms,
• opportunistic infections,
• psoriasis,
• pyelonephritis,
• reactivation of HBV,
• sarcoidosis,
• seizures, and
• neuropathy.

How to Administer Certolizumab (Cimzia)?

How to monitor:

• Monitor the functional status and improvement of symptoms.
• Perform Blood CP with differentials for cytopenias and hematological malignancies.
• Screen for Tuberculosis and Hepatitis B prior to therapy and reactivation during treatment
• Monitor for features and evidence of heart failure
• Monitor for hypersensitivity reactions, features of autoimmunity (lupus-like syndrome), and malignancies (visceromegaly, lymphadenopathy, night sweats, and weight loss).
• Examine the skin periodically for skin cancers

Mechanism of action of Certolizumab (Cimzia):

• Certolizumab is a pegylated monoclonal monoclonal humanized antibody Fab fragment which binds to the TNF alpha protein and inhibits it selectively.
• It suppresses the immune reaction mediated by TNF alpha. It lacks the Fc area, so it doesn't activate the complement system, T-cell-mediated cytotoxicity and apoptosis.

Bioavailability is 80% after subcutaneous injection

Half-life elimination is 14 days

Time to peak plasma levels is 54 to 171 hours

International Brands of Certolizumab (Cimzia):

Pricing: US

• Kit (Cimzia Prefilled Subcutaneous)
  • 2 X 200 mg/mL (per each): $5,192.92
• Kit (Cimzia Starter Kit Subcutaneous)
  • 6 X 200 mg/mL (per each): $5,192.92
• Kit (Cimzia Subcutaneous)
  • 2 X 200 mg (per each): $5,192.92

Certolizumab (Cimzia) Brands in Pakistan:

Not available in Pakistan