Is it safe to start or continue adalimumab (Humira) in a pregnant woman with an autoimmune disease, and what are the recommendations regarding timing of discontinuation, breastfeeding, and withholding live vaccines in the newborn?

Adalimumab Use During Pregnancy

Primary Recommendation

Continue adalimumab throughout pregnancy to maintain disease remission in women with autoimmune diseases, as the benefits of disease control substantially outweigh theoretical fetal risks. 1, 2

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Starting vs. Continuing Therapy

Continuing Adalimumab

• Strongly recommended to continue adalimumab before and during pregnancy for women already on therapy with rheumatic or inflammatory bowel diseases 1, 2
• The Toronto Consensus provides a strong recommendation to maintain therapy throughout all trimesters because active, uncontrolled disease poses greater maternal and fetal risks than medication exposure 2, 3
• Meta-analyses show no increased risk of adverse pregnancy outcomes, congenital abnormalities, preterm birth, or low birth weight with continued adalimumab exposure 3, 4, 5

Starting Adalimumab

• While guidelines focus on continuation rather than initiation, the evidence supporting safety of first-trimester exposure suggests starting therapy is reasonable when disease control requires it 1, 2
• Adalimumab has minimal placental transfer until the second trimester, making periconception and early pregnancy exposure lower risk 1, 2

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Timing of Discontinuation (If Pursued)

Discontinuation should only be considered in highly selected, low-risk patients meeting ALL of the following criteria: 2

1. Sustained symptomatic remission for ≥12 months before conception
2. No active disease on pre-conception endoscopy or imaging
3. No prior secondary loss of response or dose escalation
4. Documented therapeutic drug levels
5. No prior intestinal resections
6. No hospitalizations in the preceding 36 months

When to Stop (If Criteria Met)

• Last dose at 22–24 weeks gestation (alternatively 34–36 weeks in some protocols) 2
• Critical caveat: Discontinuation increases relapse risk by approximately 32% within 3 weeks postpartum, and there is no evidence that stopping at 22–24 weeks meaningfully reduces placental transfer 3
• Modifying third-trimester dosing timing does not reduce fetal drug exposure based on current pharmacokinetic data 2, 3

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Placental Transfer and Neonatal Drug Levels

• Adalimumab (IgG1 construct) crosses the placenta primarily in the third trimester, resulting in infant:mother drug concentration ratios of approximately 1.21:1 at birth 1, 6
• Mean time to drug clearance in infants is 4.0 months (range up to 12 months) 6
• Infants should be considered immunosuppressed for 6–12 months after birth if third-trimester exposure occurred 2, 3, 6

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Live Vaccine Restrictions in Newborns

Avoid all live or live-attenuated vaccines in exposed infants until adalimumab is undetectable, which may require 6–12 months after birth. 2, 3, 6

Rationale

• Case reports document fatal disseminated BCG infection in an infant vaccinated at 3 months whose mother received anti-TNF therapy throughout pregnancy 2
• Severe neonatal neutropenia has been reported, though rare 3
• Delay rotavirus, MMR, varicella, and BCG vaccines until drug clearance is documented or 12 months have elapsed 3, 6

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Breastfeeding

Adalimumab is compatible with breastfeeding. 3

• Large monoclonal antibodies have minimal transfer into breast milk and poor oral bioavailability 3
• The American College of Rheumatology supports continuation during lactation 1

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Infection Risk

• Continuing adalimumab throughout pregnancy does not increase maternal or fetal infection risk compared to unexposed patients with inflammatory bowel disease 3
• Active, uncontrolled disease poses substantially greater infection risk than medication exposure 3
• Systematic reviews of >50 studies found no increased infection risk in children exposed in utero 3
• Important exception: Combination therapy with adalimumab plus thiopurines increases infant infection risk 2.7-fold compared to adalimumab monotherapy (95% CI 1.09–6.78) 6

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Common Pitfalls to Avoid

1. Do not routinely discontinue adalimumab solely because of pregnancy – this precipitates disease flares that harm both mother and fetus more than medication exposure 2, 3

2. Do not assume third-trimester dose timing modifications reduce placental transfer – current evidence does not support this practice 2, 3

3. Do not allow live vaccines in exposed infants before 12 months unless drug clearance is documented – fatal infections have occurred 2, 6

4. Do not overlook the 32% relapse risk when discontinuing therapy, even in patients meeting all low-risk criteria 3

5. Do not combine with thiopurines during pregnancy unless absolutely necessary, as this nearly triples infant infection risk 6