Is Adalimumab safe while breastfeeding?

Summary of use during breastfeeding

Maternal adalimumab injections produce low levels in breastmilk. Because adalimumab is a large protein molecule, it is likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal.[1] Adalimumab was undetectable in the serum of some breastfed infants and adalimumab does not adversely affect the development of breastfed infants or increase the risk of infections. Waiting for at least 2 weeks postpartum to resume therapy suspended during pregnancy may minimize transfer to the infant.[2] However, in infants of mothers who received adalimumab during late pregnancy, continued use while breastfeeding does not prolong adalimumab elimination by the infant.[3] Numerous experts and professional guidelines have stated that adalimumab is a low risk to the nursing infant and acceptable to use during breastfeeding.[4-10] Anti-TNF agents reduce the levels of tumor necrosis factor and IP-10 in the milk of mothers with inflammatory bowel disease in the early postpartum period.[11] This reduction in TNF might lead to decreased milk production, so extra lactation support might be necessary in women taking adalimumab.

Effects on the breastfed infant

One woman with Crohn's disease received adalimumab 40 mg subcutaneously every week during pregnancy and breastfeeding (extent not stated). Her infant demonstrated normal growth and development at 6 months of age.[16] The authors reported a brief follow-up stating that the woman also breastfed her second infant during adalimumab therapy with no adverse consequences.[17]

Another woman with Crohn's disease received adalimumab 40 mg subcutaneously every 2 weeks during pregnancy and breastfeeding (extent not stated). Her infant demonstrated normal growth and development at 6 months of age.[18]

Two women nursed their infants (extent not stated) while receiving adalimumab 40 mg subcutaneously at unstated intervals for inflammatory bowel disease. They breastfed for at least 21 weeks and 8 weeks, respectively, but the total duration was not stated. At 14.5 and 15 months of age, respectively, neither infant had any signs of adverse drug reactions, allergic reactions or severe infections leading to hospitalization. Developmental milestones were reached on time by both infants.[13]

A pregnant woman received adalimumab 40 mg every 2 weeks for Crohn's disease until week 16 of pregnancy. Her infant was exclusively breastfed until 4 months of age, and the drug was reinstituted on day 24 postpartum. At 7 months of age, the infant was healthy with normal growth and development. The infant had no infections requiring antibiotics or hospitalization.[15]

A case-control study of women with chronic arthritic conditions found 2 women who received adalimumab during pregnancy and lactation (extent not stated). No differences were observed in the 2 infants' growth parameters, developmental milestones, vaccinations and diseases in the first year of life compared to those not exposed to the drugs with lactation.[19]

A woman receiving adalimumab for severe psoriasis breastfed 2 infants following 2 pregnancies. No adverse effects were reported in the infant, although the dosage of adalimumab and the extent of breastfeeding were not reported.[20]

In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 99 women received adalimumab while breastfeeding their infants. Among those who received adalimumab or another biologic agent while breastfeeding, infant growth, development or infection rate was no different from infants whose mothers received no treatment. An additional 68 women received a biologic agent plus a thiopurine. Infant outcomes were similar in this group.[14]

A national prospective registry of patients with rheumatic diseases who were treated with biological DMARDs was conducted in Spain. One whose mother was taking adalimumab was breastfed (extent not stated) with no mild or severe adverse events reported in the infant.[21]

A multicenter, retrospective observational study in France reported the outcomes of infants who were breastfed by mothers taking a TNF inhibitor during pregnancy or postpartum for inflammatory bowel disease. Of 153 women who continued anti-TNF therapy postpartum, 55 were taking adalimumab. The exact number of the infants breastfed during maternal adalimumab therapy was not stated. Of the 153 cases, 68 breastfed their infants for a mean duration of 61 days (range 31 to 111 days). Thirty of the breastfed infants were born to mothers who had received an ant-TNF agent after 26 weeks of pregnancy and were likely born with blood levels of the agent. None of the breastfed infants had any infectious complications.[22]

A multicenter study in Spain prospectively followed women treated for inflammatory bowel disease with biological agents, mostly anti-TNF agents. Overall, 29% of infants exposed to a biologic agent were also exposed to azathioprine or mercaptopurine and almost all were exposed during both pregnancy and lactation. Thirty-one infants were exposed to adalimumab during lactation for a mean duration of 39.8 weeks. No adverse impact of biologics was found on the psychomotor development of infants for up to 1 year of age.[23]

Effects on milk supply

Fifty-seven lactating women, 26 with inflammatory bowel disease (IBD) and 31 without had tumor necrosis factor (TNF) and chemokines (IP-10, MCP-1, and MIP-1β) measured at 2 to 6 weeks postpartum (early lactation) and again at 11 to 16 weeks (mid-lactation) postpartum. The women with IBD who were receiving either adalimumab (n = 5) or infliximab (n = 4) had lower levels of TNF and interferon gamma-induced protein 10 (IP-10) in their milk in early lactation sampling than women with IBD who were not taking a TNF inhibitor. No differences were found between either IBD group and women without IBD at either time point nor between any of the groups at mid-lactation.[11]

An analysis of the US Food and Drug Administration’s FAERS database of 7,022 spontaneous adverse reaction reports of anti-TNF drugs found that they may cause an increased risk of lactation insufficiency and disorders. Drugs that were studied included adalimumab, infliximab, golimumab, certolizumab, and etanercept. The authors noted that TNF alpha is involved in milk production, adding biological plausibility to the findings.[24]

Levels in milk

Maternal Levels. One woman received a single 40 mg of adalimumab subcutaneously at 4 weeks postpartum. Milk samples were obtained every 2 days for 8 days. A peak milk adalimumab level of 31 mcg/L was detected on day 6 after injection. Milk levels on days 5 and 8 were about 10 mcg/L.[12]

Two women received adalimumab 40 mg subcutaneously for treatment of inflammatory bowel disease at unstated intervals. The first woman received the drug during pregnancy and postpartum. At 21 weeks postpartum and 7 days after the previous dose, her breastmilk adalimumab was 4.83 mcg/L while her serum level was 6.7 mg/L. In the second woman, the milk adalimumab concentration at 8 weeks postpartum and 9 days after the last dose was 4.88 mcg/L with a simultaneous serum concentration of 5.5 mg/L.[13]

In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 21 women receiving adalimumab provided milk samples at 1, 12, 24, and 48 hours after drug administration. Some also provided samples at 72, 96, 120, and 168 hours after drug administration. Two of the women had detectable (>0.01 mg/L) adalimumab levels in milk. Peak concentrations in breastmilk were 0.45 and 0.71 mg/L and occurred at 12 to 24 hours after the dose. Seven women had undetectable milk adalimumab levels over a week of monitoring.[14]

Infant Levels. A woman received adalimumab 40 mg subcutaneously at unstated intervals while breastfeeding (extent not stated). At 8 weeks postpartum and 9 days after the prior dose, the infant had an undetectable (<0.65 mcg/L) adalimumab serum concentration.[13]

A pregnant woman received adalimumab 40 mg every 2 weeks for Crohn's disease until week 16 of pregnancy. Her infant was exclusively breastfed until 4 months of age, and the drug was reinstituted on day 24 postpartum. At 3 months of age, adalimumab was undetectable in the infant's serum.[15]

Alternatives LactMed lists

• Phototherapy
• Etanercept
• Infliximab

Adalimumab in pregnancy

LactMed covers breastfeeding only. For what the NHS and the US prescribing label say about pregnancy, see:

• Is adalimumab safe in pregnancy and breastfeeding?