NOTE: The discussion of safety / adverse effects herein focusses on key topics, and is NOT exhaustive.  Please consult the official product monograph. 

MECHANISM OF ACTION

  • Among the anti-TNF biologics, Certolizumab is unique in that it is the PEGylated Fab’ fragment of humanised monoclonal antibody to Tumour Necrosis Factor alpha (TNF-alpha). Certolizumab binds to and selectively neutralizes TNF-alpha activity.

INDICATIONS

  • Rheumatoid arthritis (RA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), psoriasis (PsO), Crohn’s Disease (CD; not in Canada)

ADULT DOSING

  • RA, PsA, AS
    • Initial loading doses: 400 mg SubQ at 0, 2, 4 weeks followed by maintenance
    • Maintenance: 200 mg SubQ every 2 weeks, or 400 mg SubQ every 4 weeks.
  •  PsO
    • 400 mg SubQ every 2 weeks
    • 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.
  •  CD (not indicated in Canada)
    • Initial loading doses: 400 mg SubQ at 0, 2, 4 weeks followed by maintenance
    • Maintenance: 400 mg SubQ every 4 weeks

DOSE ADJUSTMENT

 Hepatic Impairment: No dose adjustments provided in product monograph

 Renal Impairment: No dose adjustments provided in product monograph. Pharmacokinetics of the PEGylated component of certolizumab is expected to be dependent on renal function.

SCREENING PRIOR TO STARTING THERAPY

  •  Screening for Latent Tuberculosis: CXR, TB skin test.
    •  Patients with Latent TB (skin test ≥ 5 mm, negative CXR) must receive TB prophylaxis.  Certolizumab can be started one month after prophylaxis is started.
    •  If TB skin test is thought to be false negative (eg. high endemic risk) or false positive (eg. BCG vaccine), IGRA should be performed.
  •  Hepatitis screening: Hep B sAg, Hep B cAb, Hep C Ab

VACCINATION

Patients with chronic inflammatory / rheumatic disease have an increased risk of infection.  Vaccinations should be considered at earlier ages than that prescribed for the general population.  Ideally, the following vaccines should be considered in patients prior to starting biologics, especially patients over 50.  However, depending on disease severity, one may need to proceed with biologic therapy and vaccinate along the way (most frequent scenario in clinical practice).  Data suggests reduced vaccine response (antibody titres) while on some DMARDS / Biologics, but this has not been shown to result in increased risk of infection.

  • Pneumonia: Prevnar 13, Pneumovax (given two months apart in this order).  If Pneumovax was received first, wait one year before giving Prevnar 13.
  • Shingles: Shingrix (two doses given 2-6 months apart; biologic can be started 2 weeks after the first dose).  Shingrix is preferred over the (older) live attenuated Zostavax vaccine.  If Zostavax is used, it must be given at least 2 weeks prior to starting biologics.
  • Annual flu vaccine

MONITORING

  •  Patients with rheumatic diseases on biologics are typically re-assessed clinically every 3-6 months, with investigations performed as clinically indicated.

WHEN TO AVOID

  •  Certolizumab should be avoided in patients with active infection, active malignancy, hypersensitivity to certolizumab / components.

SIDE EFFECTS AND ADVERSE REACTIONS

  • Infection: the risk of infection is considered to be very low, but serious infections have been reported in patients on anti-TNF biologic therapy.  When considering therapy, this has to be balanced against the increased risk of infection caused by active rheumatic / inflammatory disease.  Risk of infection is also confounded by use of concomitant DMARDS and prednisone.  Advise patients with symptoms of infection to hold the biologic, seek medical attention,and do not resume until one week after recovery.
  • Reactivation of Latent TB (see above), Hepatis B reactivation
  • Malignancy: Except for a 2-3 fold increase in the risk of skin cancer (melanoma and non-melanoma), data suggests that there is no increase in the risk of solid tumours with anti-TNF biologics.  Registry data suggests that the risk of lymphoma is driven by the underlying disease, and not by biologic medications.
  • Rare reports of demyelinating disease, autoimmune (lupus-like) diseases, interstitial lung disease, congestive heart failure (especially patients with preceding class III/IV heart failure)

PREGNANCY

  • Emerging evidence suggests that Certolizumab is safe in pregnancy, and current practice is to continue it throughout pregnancy.  In general, the risk of untreated rheumatic disease to the developing fetus and to maternal health is considered to be greater than the risk of Golimumab itself.
  • Due to the large molecular size from PEGylation, placental transfer of certolizumab pegol is minimal (Förger 2016; Mariette 2018).  However, live attenuated vaccines must be avoided in the newborn for the first 6 months.

LACTATION

  • Certolizumab may be present in breast milk.  However, anti-TNF biologics are considered compatible with breastfeeding.