Is certolizumab (Cimzia) safe for use in pregnant patients with systemic lupus erythematosus (SLE)?

From the Guidelines

Certolizumab is strongly recommended for continuation prior to and during pregnancy in patients with systemic lupus erythematosus (SLE) due to its minimal placental transfer and significant benefit in controlling disease activity. The 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases conditionally recommends continuing tumor necrosis factor inhibitor therapy with certolizumab prior to and during pregnancy 1. This recommendation is based on the unique structure of certolizumab, which does not contain an Fc chain and thus has minimal placental transfer, reducing fetal exposure 1.

Key Considerations

• Certolizumab's minimal placental transfer makes it a preferred TNF inhibitor for use during pregnancy when treatment is necessary 1.
• The recommended dosing for certolizumab in pregnancy is typically 400 mg initially, followed by 200 mg every two weeks, which can be continued throughout pregnancy if needed to control lupus symptoms.
• Patients should be aware that while the risk appears low, long-term safety data in pregnancy is still limited, and close monitoring of both mother and fetus is recommended throughout pregnancy 1.
• The decision to use certolizumab should be made on a case-by-case basis, weighing the potential benefits of controlling lupus activity against any possible risks.

Important Safety Considerations

• Certolizumab, like other biologics, may increase the risk of infections, and patients should be screened for tuberculosis and other infections before starting treatment and monitored closely during pregnancy.
• The benefits of certolizumab in controlling SLE activity must be carefully weighed against the potential risks, and patients should be closely monitored for any adverse effects throughout pregnancy 1.

From the FDA Drug Label

Animal reproduction studies have been performed in rats during organogenesis at intravenous doses up to 100 mg/kg (about 2.4 times the recommended human dose of 400 mg, based on the surface area) and have revealed no evidence of harm to the fetus due to cTN3 PF. Due to its inhibition of TNFα, CIMZIA administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant [see Use in Specific Populations (8.1)].

Safety in Pregnant Patients with SLE:

• The FDA drug label does not provide direct information on the safety of certolizumab (Cimzia) in pregnant patients with systemic lupus erythematosus (SLE) specifically.
• However, animal reproduction studies in rats showed no evidence of harm to the fetus.
• The label warns that CIMZIA administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant.
• Key Considerations:
  • No direct evidence of safety in pregnant SLE patients
  • Potential impact on immune responses in newborns and infants
  • Animal studies suggest no harm to the fetus, but may not be directly applicable to human SLE patients
• Clinical Decision: Given the lack of direct evidence, certolizumab should be used with caution in pregnant patients with SLE, and the potential benefits and risks should be carefully weighed 2, 2.

From the Research

Safety of Certolizumab in Pregnant Patients with SLE

• Certolizumab pegol is recommended in women who are planning to conceive, and guidelines indicate it as a possible treatment during pregnancy 3.
• The drug has minimal placental permeability, making it a safer alternative for use in pregnant patients 3, 4.
• A case series of 13 patients with rheumatic diseases treated with certolizumab during late pregnancy showed low drug levels in cord blood, but a possible risk for maternal infections 4.
• A multicentre study of women with uveitis who received certolizumab pegol during pregnancy found the drug to be effective and safe, with no congenital malformations or infections observed in neonates 5.

Considerations for Use in Pregnancy

• Certolizumab pegol can be used in pregnant women with uveitis, with a corticosteroid-sparing effect and no observed adverse effects on the fetus 5.
• The use of certolizumab pegol in pregnancy should be considered and discussed with patients, taking into account the available safety data and the risk-benefit profile 6.
• Women with SLE who are pregnant or planning to conceive can be treated with certolizumab pegol, but should be closely monitored for potential maternal infections and other adverse effects 4, 5.