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Baricitinib
Olumiant® (baricitinib) tablets
1mg, 2mg, 4mgbaricitinib
1mg, 2mg, 4mgThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Can OLUMIANT® (baricitinib) be used in patients who are pregnant or breastfeeding?
The effects of baricitinib on human fetal development are not known and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Breastfeeding is not recommended during baricitinib treatment.
See important safety information, including boxed warning, in the attached prescribing information.
BARICITINIB is not approved for atopic dermatitis indication. Please see prescribing information for approved indications.
Olumiant® Prescribing Information
Use During Pregnancy
Based on the findings from animal reproduction studies, baricitinib may cause fetal harm during pregnancy. Available data from clinical trials and postmarketing case reports with baricitinib exposure in pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1
There are no human data on chronic baricitinib exposure throughout pregnancy. There are risks to the mother and the fetus associated with rheumatoid arthritis in pregnancy.1
The background risks of major birth defects and miscarriage for the indicated population(s) are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively.1
Report pregnancies to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979). 1
Clinical Considerations
Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.1
Use During Lactation
Lactation studies have not been conducted to assess the
- presence of baricitinib in human milk
- effects on the breastfed infant, or
- effects on milk production.1
A single oral dose of 25 mg/kg radiolabeled baricitinib was administered to lactating female Sprague-Dawley rats on postpartum day 13. Drug exposure was approximately 45-fold greater in milk than in plasma based on AUC0-t values.1
Because of the potential for serious adverse reactions in nursing infants, advise an women not to breastfeed during treatment with baricitinib and for 4 days after the last dose (approximately 5 to 6 elimination half-lives).1
Use in Individual of Reproductive Potential
Based on animal studies, baricitinib may cause fetal harm when administered during pregnancy. Consider pregnancy planning and prevention for females of reproductive potential.1
Women of reproductive potential should take appropriate precautions to avoid becoming pregnant during treatment with baricitinib and for at least 1 week after the final baricitinib treatment.2
Nonclinical Data Regarding Pregnancy and Lactation
Reproductive Toxicity in Animals
Animal Embryo-Fetal Development
In an embryofetal development study in pregnant rats, dosed orally during the period of organogenesis from gestation days 6 to 17, baricitinib was teratogenic (skeletal malformations that consisted of bent limb bones and rib anomalies) at exposures equal to or greater than approximately 11 times the maximum recommended human dose (MRHD) (on an area under the curve [AUC] basis at maternal oral doses of 10 mg/kg/day and higher).1
No developmental toxicity was observed in rats at an exposure approximately 2 times the MRHD (on an AUC basis at a maternal oral dose of 2 mg/kg/day).1
In an embryofetal development study in pregnant rabbits, dosed orally during the period of organogenesis from gestation days 7 to 20, in the presence of maternal toxicity at an exposure approximately 46 times the MRHD (on an AUC basis at a maternal oral dose of 30 mg/kg/day) observations included
- embryolethality
- decreased fetal body weights, and
- skeletal malformations (rib anomalies).1
Embryolethality consisted of increased post-implantation loss that was due to elevated incidences of both early and late resorptions.1
No developmental toxicity was observed in rabbits at an exposure approximately 7 times the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).1
It is unknown if baricitinib crosses the human placenta. In animal studies, following a 25-mg/kg dose of radioactivity-labeled [14C]-baricitinib in pregnant rats, it has been observed that radioactivity was widely distributed to both maternal and fetal tissues, confirming transfer of [14C]-baricitinib across the placenta in pregnant rats.2
Animal Prenatal and Postnatal Development
In a pre- and post-natal development study in pregnant female rats dosed orally from gestation day 6 through lactation day 20, at exposures approximately 24 times the MRDH (on an AUC basis at a maternal oral dose of 25 mg/kg/day) adverse findings observed in pups included
- decreased survival from birth to post-natal day 4 (due to increased stillbirths and early neonatal deaths)
- decreased birth weight
- decreased body weight gain during the pre-weaning phase
- developmental delays (that may be secondary to decreased body weight gain)
- increased incidence of malrotated forelimbs during the pre-weaning phase, and
- decreased cytotoxic T cells on PND 35 with recovery by PND 65.1
No developmental toxicity was observed in rats at an exposure approximately 5 times the MRHD (on an AUC basis at a maternal oral dose of 5 mg/kg/day).1
The no observed adverse effect level (NOAEL) was 25 mg/kg based on prenatal and postnatal development rat studies.2
Fertility Studies in Animals
In a combined male and female rat fertility study, baricitinib decreased overall mating performance as evidenced by decreased fertility and conception indices. In female rats there were
- increased post-implantation losses, and
- decreased numbers of mean viable embryos per litter.1
The NOAEL was 5 mg/kg (approximately 6 times the MRHD on an AUC basis) for female fertility and early embryonic development based on rat studies.1
The NOAEL for male fertility was 15 mg/kg (approximately 13 times the MRHD on an AUC basis) based on rat studies.1
Juvenile Development Studies in Animals
In a juvenile rat development study, there were
- decreased body weight at the doses of 5 and 25 mg/kg doses
- decreased immune response at dose exposures ≥5 mg/kg dose, and
- effects on bone at the 25 mg/kg dose.2
Safety monitoring measures assessing immune, growth, and bone effects are ongoing in pediatric clinical studies.2
In a juvenile rat development study, baricitinib had no adverse effects on clinical signs, sexual maturation, ophthalmology, behavioral performance, or reproductive performance.2
Clinical Data Regarding Pregnancy and Lactation
Exclusion and Permanent Discontinuation Clinical Trial Criteria Related to Pregnancy
Patients were excluded from participating in baricitinib clinical studies if they were
- pregnant or nursing at the time of study entry
- women of childbearing potential who did not agree to use 2 forms of effective birth control when engaging in sexual intercourse while enrolled in the study and for at least 28 days following the last dose of study treatment, or
- men who did not agree to use 2 forms of effective birth control while engaging in sexual intercourse with female partners of childbearing potential while enrolled in the study, and for at least 28 days following the last dose of study treatment.2
Pregnancy was a criterion for permanent discontinuation in all baricitinib clinical studies.2
Pregnancies in Baricitinib Clinical Trials and Post-marketing Reporting
A total of 117 pregnancies were reported with baricitinib use in clinical trials and postmarketing across rheumatoid arthritis, atopic dermatitis, and alopecia areata indications. provides details on maternal and paternal exposures.3
Indication |
|
Maternal Age, years |
||||
Rheumatoid Arthritis |
Atopic Dermatitis |
Alopecia Areata |
No Indication Reported |
|||
All pregnancies, n |
66 |
30 |
9 |
12 |
117 |
NA |
Clinical trial pregnancies |
||||||
Maternal exposure, n |
25a |
12b |
8b |
0 |
45 |
32 (17-43)c |
Live births, n (%) |
12 (48.0) |
5 (41.7) |
1 (12.5) |
0 |
18 (40.0) |
32 (25-43) |
Spontaneous abortions, n (%) |
7 (28.0) |
1 (8.3) |
2 (25.0) |
0 |
10 (22.2) |
32 (20-40) |
Elective terminations, n (%) |
2 (8.0) |
3 (25.0) |
2 (25.0) |
0 |
7 (15.6) |
34 (24-36) |
Lost to follow-up or still in utero, n (%) |
4 (16.0) |
3 (25.0) |
3 (37.5) |
0 |
10 (22.2) |
32 (17-40) |
Paternal exposure, n |
3 |
14 |
1 |
0 |
18 |
NA |
Live birth, n (%) |
3 (100.0) |
5 (35.7) |
1 (100.0) |
0 |
9 (50.0) |
NA |
Spontaneous abortions, n (%) |
0 |
3 (21.4) |
0 |
0 |
3 (16.7) |
NA |
Elective terminations, n (%) |
0 |
0 |
0 |
0 |
0 |
NA |
Lost to follow-up or still in utero, n (%) |
0 |
6 (42.9) |
0 |
0 |
6 (33.3) |
NA |
Postmarketing pregnancies |
||||||
Maternal exposure, n |
37d |
2e |
0 |
12f |
51 |
35 (24-49)g |
Live births, n (%) |
6 (16.2) |
0 |
0 |
1 (8.3) |
7 (13.7) |
36 (27-43) |
Spontaneous abortions, n (%) |
3 (8.1) |
1 (50.0) |
0 |
0 |
4 (7.8) |
36 (32-37) |
Elective terminations, n (%) |
2 (5.4) |
0 |
0 |
0 |
2 (3.9) |
45 |
Lost to follow-up or still in utero, n (%) |
26 (70.3) |
1 (50.0) |
0 |
11 (91.7) |
38 (74.5) |
34 (24-49) |
Paternal exposure, n |
1 |
2 |
0 |
0 |
3 |
NA |
Live births, n (%) |
0 |
0 |
0 |
0 |
0 |
NA |
Spontaneous abortions, n (%) |
0 |
0 |
0 |
0 |
0 |
NA |
Elective terminations, n (%) |
0 |
0 |
0 |
0 |
0 |
NA |
Lost to follow-up or still in utero, n (%) |
1 (100.0) |
2 (100.0) |
0 |
0 |
3 (100.0) |
NA |
Abbreviations: AA = alopecia areata; AD = atopic dermatitis; DMARD = disease-modifying antirheumatic drug; MTX = methotrexate; RA = rheumatoid arthritis.
Data is through April 30, 2022
aRA patients concomitant therapies: baricitinib as monotherapy, n=6; baricitinib with MTX n=12; baricitinib with MTX + DMARDs, n=4 (n=1 hydroxychloroquine, n=2 leflunomide, n=1 sulfasalazine); baricitinib with DMARD, n=1 (hydroxychloroquine). baricitinib with DMARDs n=2, (detailed type not reported). The dose of baricitinib was 4-mg in most cases.
bAll patients received baricitinib as monotherapy in AD and AA clinical trials. The dose of baricitinib was 4-mg in most cases.
cThere were 4 patients of unknown age; 2 live births, and 2 elective terminations.
dRA patients concomitant therapies: baricitinib as monotherapy, n=7; baricitinib with MTX n=2; baricitinib with DMARDs n=7, (n=2 certolizumab, n=2 hydroxychloroquine, n=1 leflunomide, n=1 leflunomide + sulfasalazine, n=1 tocilizumab); baricitinib with MTX + DMARDs, n=1 (n=1 hydroxychloroquine, golimumab); concomitant use of DMARDs not reported, n=20. The dose of baricitinib was 4-mg in most cases with information provided.
eConcomitant DMARD use not reported.
fBaricitinib as monotherapy, n=1; baricitinib with MTX, n=1; baricitinib + DMARDs, n=2 (n=1 hydroxychloroquine, n=1 sulfasalazine); information on concomitant use of DMARDs not reported, n=8. The dose of baricitinib was 4-mg in most cases with information provided.
gPatients of unknown age, n=15 (n=1 for live births, n=1 for spontaneous abortions, n=1 for elective terminations, and n=12 for cases lost to follow-up or still in-utero).
Incidence of Pregnancies with Maternal Exposures During Baricitinib Clinical Trials
Data on fetal outcomes and breastfeeding were collected for all reported cases of pregnancy that occurred during maternal or paternal exposures to study treatment. An overview of total exposure and relevant baseline characteristics can be seen in .4
|
All BARI RAa |
All BARI ADb |
All BARI AAc |
BARI exposure, total patient-years |
14744.4 |
4628.4 |
2217.9 |
Baseline characteristics |
|||
Mean (SD) age, years |
52.7 (12.2) |
36.5 (13.7) |
37.5 (12.9) |
Female patients, n (%) |
2983 (79.1) |
1038 (39.4) |
804 (61.7) |
Abbreviation: AA = alopecia areata; AD = atopic dermatitis; BARI = baricitinib; RA = rheumatoid arthritis.
aData obtained from RA randomized clinical trials with data cutoff of October 21, 2020.
bData obtained from AD randomized clinical trials with data cutoff of December 21, 2021.
cData was obtained from AA randomized clinical trials BRAVE-AA1 (data cutoff May 24, 2022) and BRAVE-AA2 (data cutoff May 10, 2022).
Of the 45 clinical trial pregnancies with maternal exposures in clinical trials,
- 40 had baricitinib exposure mainly occurring during the first trimester
- 18 resulted in live birth; 2 premature delivered via caesarean section at 32 and 34 weeks of gestation
- 10 ended in spontaneous abortion; 9 during the first trimester and 1 during the second trimester (15th week gestation)
- 7 elective terminations; 1 due to ectopic pregnancy, all others no medical reason reported
- 7 were lost to follow-up, and
- 3 were still in utero at data cutoff.3
Among the 10 spontaneous abortions, 7 women use concomitant disease-modifying antirheumatic drug (DMARD) therapy, 2 were 38 years or older, and the median age was 32 (range 20 to 40 years).3
No congenital anomalies were identified in clinical trials.3
In addition, there was 1 pregnancy reported in the baricitinib AD clinical trial in pediatric patients aged 2 to <18 years. The patient was 17 years old and taking baricitinib 4 mg. The exposure was during the first trimester. The mother experienced a complication of spiral umbilical cord during labor but recovered. There were no reported complications in the infant.2
In the baricitinib clinical trial in patients with juvenile idiopathic arthritis, no pregnancies were reported.2
Postmarketing Reports of Maternal Exposures With Baricitinib
Of the 51 pregnancies with maternal exposure to baricitinib identified from post marketing sources
- 24 had baricitinib exposure during the first trimester; 25 exposure timing were unknown
- 7 resulted in live births; 3 were full-term, 1 was premature (gestational age unknown), and 3 were unknown
- 4 ended in spontaneous abortions (2 in the first trimester and 2 unknown), of which 3 had reported ages in their 30s with 2 patients >35 years of age
- 2 ended in elective termination; 1 due to ectopic pregnancy and 1 due to concerns over exposure to baricitinib (no fetal abnormality reported)
- 28 were lost to follow-up, and
- 10 were still in utero at data cutoff.3
Two incidences of congenital malformation were reported in patients exposed to baricitinib in the postmarketing setting.
A case of hip dysplasia was in a live birth of a full-term infant. The mother was a 31-year-old female treated for RA with baricitinib 4 mg, prior medication of leflunomide 20 mg (discontinued 4 months prior to pregnancy) and sulfasalazine 500 mg during pregnancy, beginning 2 months after baricitinib was stopped. Information regarding the infant hip dysplasia was not provided.2,3
A case of spontaneous abortion was reported as a congenital anomaly (anencephaly) in a 36-year-old female being treated for RA with baricitinib 4 mg who had a spontaneous abortion at 13.4 weeks of gestation. Concomitant medications included hydroxychloroquine, golimumab, prednisolone, methotrexate, folic acid, and ibuprofen. The fetus was exposed to baricitinib for 2 to 4.5 weeks.2,3
Incidence of Pregnancy after Paternal Exposure
Among the 21 pregnancies with paternal exposure, no congenital anomalies were reported. See for details.3
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Bergamini B, Seneschal J, Meyers KJ, et al. Pregnancy outcomes in patients exposed to baricitinib in clinical trials and during post-marketing surveillance. British Journal of Dermatology. Published online Aug 18, 2023. https://doi.org/10.1093/bjd/ljad279
4Thyssen JP, Seneschal J, Bhoja P, et al. Pregnancy outcomes in patients exposed to baricitinib in randomised clinical trials during post-marketing surveillance. Poster presented at the 7th congress of the Skin Inflammation & Psoriasis International Network (SPIN); July 6-8, 2022; Paris, France.
5Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials. J Dermatolog Treat. 2023;34(1):2161812. https://doi.org/10.1080/09546634.2022.2161812
6King B, Ohyama M, Senna Maryanne, et al. Outcomes of down-titration in patients with severe scalp alopecia areata treated with baricitinib 4-mg: week 104 data from BRAVE-AA2. Poster presented at American Academy of Dermatology Annual Meeting; March 2023; New Orleans, United States.
7Taylor PC, Takeuchi T, Burmester GR, et al. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022;81(3):335-343. https://doi.org/10.1136/annrheumdis-2021-221276
Date of Last Review: August 28, 2023