EU Approves Cimzia for Pregnant and Breastfeeding Women with a Rheumatic Disease

The European Union has expanded its approval of the rheumatic disease therapy UCB’s Cimzia t0 include women who are pregnant or breastfeeding.

UCB’s treatment becomes the first anti-tumor necrosis factor (TNF) therapy to cover these patients. The label change was approved by the European Medicines Agency. TNF is a pro-inflammatory cytokine, or molecule released by immune cells, and a major therapeutic target in inflammatory diseases.

The approval follows positive results from UCB’s completed CRIB (NCT02019602) and CRADLE (NCT02154425) Phase 1 clinical trials. The studies’ design represented a major improvement over historical anti-TNF data, which had been based on case reports. CRIB and CRADLE enrolled women with axial spondyloarthritis (axSpA, which includes ankylosing spondylitis), rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease.

CRIB assessed the potential transfer of Cimzia’s active ingredient, certolizumab pegol (CZP), from pregnant women to their fetuses. Investigators studied 16 women who were receiving CZP at least 30 weeks. CZP values were assessed at birth and at weeks four and eight.

Results showed no to minimal transfer of CZP through the placenta. In addition, researchers did not detect anti-CZP antibodies in mothers, umbilical cords, or infants. And analysis of adverse effects did not raise serious safety concerns.

The CRADLE trial primarily assessed the amount of CZP in maternal breast milk and the daily dose of maternal CZP ingested by the infant.

A total of 137 breast milk samples from 17 mothers were collected. All samples showed minimal CZP concentrations. Analysis of CZP potentially ingested by the infant also led to minimal values (0.04 to 0.30 percent). Experts consider a value lower than 10 percent not to be of concern to an infant’s wellbeing.

Similarly to CRIB, adverse effects in mothers studied in CRADLE were consistent with the safety profile of CZP. Infants showed similar side effects as controls not exposed to Cimzia.

UCB also analyzed data from more than 500 mothers who took Cimzia during their pregnancy, including more than 400 during the first trimester. Results did not suggest that Cimzia caused any fetus malformations. However, due to the limited clinical experience, Cimzia should only be used during pregnancy if clinically needed, the company advised.

“Women frequently discontinue their anti-TNF treatment throughout pregnancy, a time when disease control is essential to ensure optimal infant and maternal health,” Xavier Mariette, head of the rheumatology department at Bicetre Hospital, Paris-Sud University, said in a press release.

Cimzia, a medication injected under the skin, is the first approved TNF blocker that demonstrated minimal transfer from mother to infant during pregnancy, Mariette said.

“Today’s label change for Cimzia is important for many European women who need treatment options to manage their chronic rheumatic disease without compromising their plans for pregnancy and breastfeeding,” added Emmanuel Caeymaex, executive vice president and head of the Immunology Patient Value Unit at UCB.

Symptoms of chronic rheumatic diseases, such as axial spondyloarthritis and rheumatoid arthritis, often appear first in women of childbearing age. An active rheumatic disease in pregnancy can seriously affect both mother and infant. It increases the risk of miscarriage, preterm delivery, smaller infant size, and need for a caesarean.

Importantly, about 50% of women with chronic rheumatic disease require therapeutic intervention. The disease and the possible therapies for treating it have generated serious concerns over the baby’s health and nutritional well-being during pregnancy and during breastfeeding.