Can a pregnant woman with a severe autoinflammatory disease such as Cryopyrin‑Associated Periodic Syndromes, systemic juvenile idiopathic arthritis, or refractory rheumatoid arthritis safely continue anakinra (interleukin‑1 receptor antagonist, 100 mg subcutaneously daily) or should it be discontinued?

Anakinra in Pregnancy

Anakinra should be continued throughout pregnancy in women with severe autoinflammatory diseases such as CAPS, systemic JIA, or refractory rheumatoid arthritis, because maintaining disease control provides greater maternal and fetal benefit than any theoretical risk from drug exposure. 1

Primary Recommendation

• The 2021 EULAR/ACR guidelines explicitly state that anakinra is the preferred IL-1 blocking agent during pregnancy among all anti-IL-1 therapies, supported by regulatory advice and clinical case series. 1

• A benefit-risk discussion should occur before conception, weighing the documented harms of uncontrolled autoinflammatory disease (preterm delivery, intrauterine growth restriction, pregnancy loss) against the limited but reassuring safety data for anakinra. 1

Evidence Supporting Continuation

• Clinical case series demonstrate successful pregnancy outcomes: 15 pregnancies in women with CAPS who continued anakinra showed no preterm births or serious complications, with persistent symptom relief and prevention of long-term disease sequelae. 2

• An additional prospective cohort of 5 pregnancies with anakinra exposure (for adult-onset Still's disease and systemic JIA) resulted in full-term singleton live births with no major or long-term complications. 3

• Four pregnancies in women with familial Mediterranean fever treated with anakinra throughout gestation showed normal fetal development and unremarkable early childhood outcomes. 4

FDA Labeling and Safety Data

• The FDA label states that available retrospective studies and case reports are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal events. 5

• Animal reproduction studies in rats and rabbits at doses up to 25 times the maximum recommended human dose revealed no evidence of fetal harm. 5

• The FDA emphasizes that risks to mother and fetus from uncontrolled rheumatoid arthritis or CAPS (including preterm delivery, low birth weight, small for gestational age) must be weighed against theoretical drug risks. 5

Specific Clinical Scenarios

Dosing During Pregnancy

• Continue the pre-pregnancy anakinra dose (typically 100 mg subcutaneously daily) throughout gestation; dose escalation may be required if disease activity increases, as demonstrated in one twin pregnancy. 2

• The subcutaneous and intravenous routes are comparable in efficacy; route selection should be based on patient preference and clinical characteristics. 6

Disease Flare Risk with Discontinuation

• Discontinuing anakinra risks maternal disease flares that can harm both mother and fetus through systemic inflammation, fever, and associated complications (oligohydramnios, pregnancy-induced hypertension). 3

• Two of five women who discontinued anakinra required steroid escalation for disease flares, and two developed oligohydramnios—a complication potentially linked to both fetal renal anomalies and uncontrolled maternal hyperthermia. 3

Important Caveats and Monitoring

Potential Renal Concerns

• One case of renal agenesis occurred in a twin pregnancy where the mother continued anakinra; however, the affected twin carried the same NLRP3 mutation as the mother, making a causal relationship with anakinra unlikely. 2

• The relationship between maternal IL-1 inhibitor use, uncontrolled maternal febrile disease, and fetal renal outcomes requires further exploration, but current evidence does not establish causation. 3

Neonatal Considerations

• Unlike TNF inhibitors (which are IgG1 antibodies with significant third-trimester placental transfer), anakinra is a small recombinant protein (17 kDa) with minimal placental passage, reducing theoretical fetal immunosuppression risk. 5

• No specific neonatal monitoring or vaccine delays are recommended for anakinra-exposed infants, in contrast to monoclonal antibody biologics. 5

Breastfeeding

• Anakinra is compatible with breastfeeding: limited clinical data show no adverse effects on breastfed infants, and at least two women successfully breastfed while continuing anakinra. 5, 3

• The developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for continued disease control. 5

Common Pitfalls to Avoid

• Do not routinely discontinue anakinra upon pregnancy confirmation in women with severe autoinflammatory disease; doing so may precipitate life-threatening maternal flares (fever, serositis, systemic inflammation) that pose greater fetal risk than continued therapy. 1, 2

• Do not confuse anakinra safety data with other biologics: anakinra has a distinct pharmacokinetic profile (small protein, short half-life, minimal placental transfer) compared to monoclonal antibodies like adalimumab or rituximab. 5

• Do not delay treatment of severe disease flares out of concern for drug exposure; uncontrolled maternal inflammation (particularly hyperthermia) carries documented risks for adverse pregnancy outcomes. 3