Drugs in Pregnancy and Lactation: Tenth Edition


Immunologic Agent (Immunomodulator)

PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk



No reports describing the use of rilonacept in human pregnancy have been located. The protein caused developmental toxicity (structural anomalies and death) in two animal species. If the agent is given shortly before or during pregnancy, the woman should be counseled as to the potential embryo–fetal risk.


Rilonacept is a dimeric fusion protein that acts as an interleukin-1 blocker. It is indicated for the treatment of cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome in adults and children ≥12 years of age. Pharmacokinetic data are not available from the manufacturer, but after weekly SC doses, steady-state concentrations were reached at 6 weeks (1). In a 2009 reference, the circulation half-life was cited as 8.6 days (2).

Reproduction studies have been conducted in cynomolgus monkeys and mice. In monkeys given doses up to about 3.7 times the human doses of 160 mg based on BSA (HD), all doses reduced serum levels of estradiol up to 64% compared with controls. In addition, all doses increased the incidence of lumbar ribs compared with both control animals and historical control incidences. The fetus of the only monkey exposed during the later period of gestation showed multiple fusion and absence of the ribs and thoracic vertebral bodies and arches. In this monkey, the exposure was below that expected clinically. A murine analog of rilonacept was used in mice. The highest dose, about 6 times higher than the HD, resulted in threefold increase in the number of stillbirths. In a perinatal and postnatal mouse study with the murine analog, all doses up to about 6 times the HD caused an increased incidence of unscheduled death in the offspring.

Neither carcinogenic nor mutagenic studies have been conducted with rilonacept. No adverse effects on fertility parameters were observed in male and female mice given multiple doses of the murine analog up to about 6 times the HD (1).

It is not known if rilonacept crosses the human placenta. The molecular weight (about 251,000) suggests that passive transfer will not occur, but the long circulation half-life will place the protein at the maternal–fetal interface for a prolonged period. Moreover, other proteins (e.g., see Immune Globulin Intravenous) cross the placenta. If the toxicity observed in the two animal species were direct effects (i.e., effects on the embryo and/or fetus and not caused by maternal effects), this would be evidence that the protein can cross hemochorial placentas.


No reports describing the use of rilonacept during human lactation have been located. The high molecular weight of this protein (about 251,000) suggests that excretion into mature breast milk will be inhibited. Because immunoglobulins and other high-molecular-weight substances are excreted into colostrum, exposure of the nursing infant to rilonacept might occur during the first few days after birth. The effect of this exposure on a nursing infant is unknown. However, in children and adult patients treated with this drug, an increase in infections is a common complication due to interference with the immune response. Nursing infants of women receiving the drug should be monitored for this effect.


1.Product information. Arcalyst. Regeneron Pharmaceuticals, 2009.

2.Kapur S, Bonk ME. Rilonacept (Arcalyst), an interleukin-1 trap for the treatment of cryopyrin-associated periodic syndromes. P&T 2009;34:138–41.