certolizumab

REMS

Moderately to severely active Crohn's disease when response to conventional therapy has been inadequate.
Moderately to severely active rheumatoid arthritis.
Active psoriatic arthritis.
Active ankylosing spondylitis.
Active polyarticular juvenile idiopathic arthritis.
Moderate to severe plaque psoriasis in patients who are not candidates for systemic therapy or phototherapy.
Active non-radiographic axial spondyloarthritis with objective signs of inflammation.

Action ⬆ ⬇

Neutralizes tumor necrosis factor, a prime mediator of inflammation; pegylation provides a long duration of action.

Therapeutic effects:

Decreased signs/symptoms of Crohn's disease.
Decreased pain and swelling, decreased rate of joint destruction, and improved physical function in rheumatoid arthritis and polyarticular juvenile idiopathic arthritis.
Decreased joint swelling and pain in psoriatic arthritis.
Decreased spinal pain and inflammation in ankylosing spondylitis.
Reduced severity of plaques.
Decreased pain and swelling, reduced C-reactive protein levels, and improved physical function in axial spondyloarthritis.

Pharmacokinetics ⬆ ⬇

Absorption: 80% absorbed following SUBQ administration.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 14 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	50–120 hr	2–4 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active infection (including localized);
Concurrent use of anakinra.

Use Cautiously in:

History of chronic or recurrent infection or underlying illness/treatment predisposing to infection;
History of exposure to tuberculosis (TB);
History of opportunistic infection;
Patients residing, or who have resided, where TB, histoplasmosis, coccidioidomycoses, or blastomycosis is endemic;
History of demyelinating disorders (may exacerbate);
History of HF;
OB: Use during pregnancy only if potential maternal benefits justify potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefits justify potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: May ↑ risk of infection in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: psoriasis, skin reactions (rarely severe)

Hemat: hematologic reactions

MS: arthralgia

Misc: infection (including reactivation TB, hepatitis B virus [HBV] reactivation, and other opportunistic infections due to bacterial, invasive fungal, viral, mycobacterial, and parasitic pathogens), HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, SERUM SICKNESS, AND URTICARIA), lupus-like syndrome, MALIGNANCY (INCLUDING LYMPHOMA, HEPATOSPLENIC T-CELL LYMPHOMA [HSTCL], LEUKEMIA, AND SKIN CANCER)

Interactions ⬆ ⬇

Drug-drug:

Anakinra↑ risk of serious infections; concurrent use contraindicated.
Concurrent use with azathioprine and/or methotrexate may ↑ risk of HSTCL.
May ↓ antibody response to or ↑ risk of adverse reactions to live vaccines; avoid concurrent use.

Route/Dosage ⬆ ⬇

Crohn's Disease

SC (Adults ): 400 mg (given as two 200-mg injections) initially; then repeat 2 and 4 wk later; may be followed by maintenance dose of 400 mg (given as two 200-mg injections) every 4 wk.

Rheumatoid Arthritis or Psoriatic Arthritis

SC (Adults ): 400 mg (given as two 200-mg injections) initially; then repeat 2 and 4 wk later; then maintenance dose of 200 mg every 2 wk (400 mg [given as two 200-mg injections] every 4 wk may be used alternatively).

Ankylosing Spondylitis or Non-Radiographic Axial Spondyloarthritis

SC (Adults ): 400 mg (given as two 200-mg injections) initially; then repeat 2 and 4 wk later; then maintenance dose of 200 mg every 2 wk or 400 mg (given as two 200-mg injections) every 4 wk.

Polyarticular Juvenile Idiopathic Arthritis

SC (Children ≥2 yr and ≥40 kg): 400 mg (given as two 200-mg injections) initially; then repeat 2 and 4 wk later; then maintenance dose of 200 mg every 2 wk (starting at Wk 6).
SC (Children ≥2 yr and 20–<40 kg): 200 mg initially; then repeat 2 and 4 wk later; then maintenance dose of 100 mg every 2 wk (starting at Wk 6).
SC (Children ≥2 yr and 10–<20 kg): 100 mg initially; then repeat 2 and 4 wk later; then maintenance dose of 50 mg every 2 wk (starting at Wk 6).

Plaque Psoriasis

SC (Adults ): 400 mg (given as two 200-mg injections) every 2 wk; Patients ≤90 kg: may consider giving 400 mg (given as two 200-mg injections) initially; then repeat 2 and 4 wk later; then maintenance dose of 200 mg every 2 wk.

Availability ⬆ ⬇

Lyophilized powder for injection: 200 mg/vial
Solution for injection (prefilled syringes): 200 mg/mL

Assessment ⬆ ⬇

Assess for signs and symptoms of improvement or progression of disease process being treated.
Assess for signs of infection prior to and during therapy. Monitor all patients for active TB (persistent cough, wasting, weight loss, low-grade fever) during therapy, even if initial test was negative. Do not begin certolizumab during an active infection. If new infection develops, monitor closely and discontinue certolizumab if infection becomes serious.
Monitor for signs of hypersensitivity reactions (angioedema, dyspnea, hypotension, rash, serum sickness, urticaria). If reactions occur, discontinue certolizumab and treat symptomatically.
Assess for signs and symptoms of systemic fungal infection. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until pathogen identified. Consult with infectious diseases specialist. Consider stopping certolizumab until infection resolved.
Monitor for signs and symptoms of lupus-like syndrome. If symptoms occur discontinue certolizumab.

Lab Test Considerations:

May cause anemia, leukopenia, pancytopenia, and thrombocytopenia.
- Monitor CBC with differential periodically during therapy. May cause anemia, leukopenia, pancytopenia, and thrombocytopenia. Consider discontinuing certolizumab if significant hematologic dyscrasias occur.
- Test for HBV infection before initiating therapy. Monitor carriers closely for clinical and lab signs of active infection during therapy and for several mo following last dose. If HBV reactivation occurs, discontinue certolizumab and initiate antiviral therapy.
- Perform test for latent TB. If positive for latent TB, active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for TB who have risk factors for tuberculosis infection, begin treatment for TB prior to starting certolizumab therapy. Monitor for TB throughout therapy, even if latent TB test is negative.
- May ↑ liver enzymes.
- May erroneously ↑ aPTT.

Implementation ⬆ ⬇

Update immunizations according to current guidelines prior to therapy.
Assess for latex allergy if using prefilled syringe. Removal cap contains natural latex derivative.
Lyophilized powder for injection: Reconstitution: Bring vial to room temperature for 30 min prior to reconstitution. Do not use other warming methods. Using the provided 20-gauge needle, add 1 mL sterile water for injection to vial. Gently swirl for 1 min; do not shake. Swirl every 5 min for up to 30 min until fully reconstituted. Solution is clear to opalescent, colorless to yellow, and free from particulates. Administer within 2 hr or refrigerate up to 24 hr prior to injection. Do not freeze.Concentration: 200 mg/mL. Using a new 20-gauge needle for each vial, withdraw reconstituted solution into two separate syringes, each containing 1 mL of certolizumab. Switch each 20-gauge needle to a 23-gauge needle prior to injection. Give 400-mg dose as two injections of 200 mg each.
SC: Bring reconstituted solution and prefilled syringes to room temperature for 30 min and no longer than 2 hr prior to injection. Inject full contents of syringe subcutaneously into separate sides of the abdomen or thigh. Avoid areas of skin tenderness, bruising, induration, scars, or stretch marks.

Patient/Family Teaching ⬆ ⬇

Advise patient of potential benefits and risks of certolizumab. Instruct patient in correct technique for injection, and care and disposal of equipment. Advise patient to read the Medication Guide prior to starting therapy.
Advise patient to avoid live vaccines during or immediately prior to initiating therapy.
Inform patient of risk of infection. Advise patient to notify health care professional if symptoms of infection (fever, cough, flu-like symptoms, open cuts or sores), including TB or reactivation of HBV infection, occur.
Counsel patient about possible risk of lymphoma and other malignancies while receiving certolizumab. Advise patient to obtain periodic skin examinations during therapy.
Advise patient to notify health care professional if signs of hypersensitivity reactions (rash, swollen face, difficulty breathing) or new or worsening medical conditions, such as heart or neurological disease or autoimmune disorders, occur and to report signs of bone marrow depression (bruising, bleeding, or persistent fever).
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage pregnant patients to enroll in the 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/.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in signs and symptoms of Crohn's disease.
Decreased pain and swelling with decreased rate of joint destruction in patients with rheumatoid arthritis.
Decreased joint swelling and pain in psoriatic arthritis.
Decreased spinal pain and inflammation in ankylosing spondylitis.
Decreased severity of plaques.
Decreased pain and swelling, decreased C-reactive protein levels, and improved physical function in axial spondyloarthritis.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇