Upadacitinib as Rescue Therapy in a Pregnant Patient With IBD

ABSTRACT

Upadacitinib is an oral Janus kinase inhibitor approved to treat moderate-to-severe ulcerative colitis. Studies have shown that upadacitinib is highly effective, though use has been limited in certain populations due to concerns of side effects. Outside of animal studies and rare case reports, there are little data for the safety of upadacitinib use in pregnancy. We report a case of a patient with left-sided ulcerative colitis recurrently exacerbated by pregnancies who responded to upadacitinib in her fourth pregnancy. Additional data will be helpful to establish the safety for Janus kinase inhibitors for treatment of inflammatory bowel disease patients during pregnancy.

INTRODUCTION

Upadacitinib is an oral Janus kinase (JAK) inhibitor approved to treat moderate to severe ulcerative colitis (UC).¹ A 2023 prospective study reported achievement of 81% clinical remission after 8 weeks on upadacitinib; all patients previously failed anti-tumor necrosis factor therapy and 89% failed 2 or more therapies.² While upadacitinib is an effective medication in the treatment of UC, its safety in specific populations remains uncertain. The data on maternal exposure to JAK inhibitors during pregnancy have been limited to animal studies, observational studies, and one case report.³ We report a case of successful upadacitinib use as rescue therapy to induce remission during pregnancy.

CASE REPORT

We present a case of a 34-year-old G4P4004 female with a history of left-sided UC since 2018. She was diagnosed with Mayo 3 colitis in the setting of hematochezia, diarrhea, and urgency. She went through multiple lines of therapy including biologics (Table 1). Her flare symptoms were often evoked by pregnancy, per fecal calprotectin and endoscopy, and she required change of therapy in her first and third pregnancies (Figure 1). With each therapy, she demonstrated endoscopic healing and deep remission.

Table 1.

Summary of patient's clinical course and prior treatments for her left-sided ulcerative colitis

Event	Flare symptoms	Calprotectin (mcg/g)	Endoscopic findings	Treatment prior to event	Treatment after event
Diagnosis	Yes	N/a	Mayo 3 colitis	None	PO/PR mesalamine (4.8 g/d, 1 g nightly)
Pregnancy #1	Yes	N/a	Mayo 2 colitis	PO/PR mesalamine	Infliximab 10 mg/kg every 8 weeks
Pregnancy #2	No	N/a	N/a	Infliximab	Infliximab
Pregnancy #3	Yes	>8,000	Mayo 2 colitis	Infliximab	Ustekinumab 90 mg every 8 weeks
Non–pregnancy-related flare	Yes	5,780	Mayo 3 colitis	Ustekinumab	Adalimumab 40 mg every 2 weeks

At diagnosis and all her flares, her symptoms included hematochezia, diarrhea, and urgency. Fecal calprotectin measurements were not done for her first 2 pregnancies. Her flares often corresponded with pregnancies.

n/a, not applicable; PO, per os; PR, per rectum.

Figure 1.

Fecal calprotectin (mcg/g) trended over 3 years in this patient. The periods that the patient was pregnant are denoted (green), as well as treatment changes. The patient developed flares in 3 of her 4 pregnancies (calprotectin was not monitored during her first 2 pregnancies). With each change in therapy, including induction with upadacitinib in pregnancy #4, a decline in her fecal calprotectin was observed and correlated with the patient's clinical symptoms.

She became pregnant with her fourth child at the end of 2023. Her early obstetric course was unremarkable with a normal fetal anatomic survey at 20 weeks. At 26 weeks, she developed urgency and bloody diarrhea with a Partial Mayo Score of 7, leading to admission for intravenous methylprednisolone at 27 weeks, 5 days. Sigmoidoscopy demonstrated Mayo 3 colitis to the sigmoid colon. Given her prior failure of anti-tumor necrosis factor and interleukin-12/23 inhibition and desire to rapidly improve her symptoms to minimize risk of flare in pregnancy, the decision was made to initiate upadacitinib 45 mg at 28 weeks. The lack of data for upadacitinib use in pregnancy and theoretical risk to organogenesis were discussed. Her calprotectin decreased from 1990 to 10 mcg/g over 3 weeks, with associated clinical improvement and decrease in Partial Mayo Score to 0 (Figure 1). Maternal glucose levels remained normal despite steroids. Fetal testing with daily nonstress tests were reassuring throughout. An inpatient ultrasound demonstrated a well-grown fetus with estimated fetal weight in the 51st percentile. She was discharged after a 5-day admission with symptom resolution.

She was induced for oligohydramnios with an amniotic fluid index of 3.9 cm and had an uncomplicated vaginal delivery at 40 weeks, 6 days of a male neonate, weighing 3,940 grams with Apgar scores of 8 and 9. Maternal and neonatal postpartum courses were unremarkable. Postpartum, the patient transitioned to golimumab due to the safety profile for breastfeeding. She remained asymptomatic with improvement in C-reactive protein and calprotectin. There were no additional concerns, and she only required a routine 6 weeks postpartum visit. Evaluation of the newborn revealed nondysmorphic appearance, without skeletal or cardiac abnormalities. His growth and development have remained normal.

DISCUSSION

Upadacitinib is contraindicated for pregnant patients due to lack of human data on maternal exposure to JAK inhibitors during pregnancy. Ehrlich et al⁴ (2025) investigated placental transfer of upadacitinib and demonstrated its presence, highlighting that research into safety in pregnancy is paramount.

Animal studies of other JAK inhibitors have noted adverse maternal and fetal outcomes. High doses of tofacitinib have demonstrated teratogenicity and feticidal effects.⁵ Baricitinib was associated with decreased fetal birth weight, embryo lethality, and skeletal malformations when in high doses.⁶

Data for other JAK inhibitors in human pregnancies are limited to case reports and post hoc analysis of early clinical trials. In one case study, tofacitinib was used as rescue therapy for refractory UC in pregnancy without reported adverse maternal or fetal outcomes.⁷ A case series of patients exposed to tofacitinib either during conception or first trimester and patients treated with tofacitinib throughout pregnancy similarly reported no adverse maternal or fetal outcomes.⁸ Mahadevan et al analyzed maternal and fetal outcomes of pregnancies with exposure to upadacitinib that were reported to AbbVie's safety database as of May 2, 2023.⁹ Of the 128 upadacitinib exposures with known outcomes, there was no evidence of teratogenicity and rates of adverse pregnancy outcomes were comparable with those of the general population.⁹

To date, data on pregnancy outcomes with JAK inhibitors are limited to exposure early in pregnancy, predominantly in the first trimester. Prior studies have evaluated the mechanism of JAK inhibitor teratogenicity and have excluded fetal mutagenic and genotoxic effects.¹⁰ The teratogenic risk may be highest during organogenesis, although more study is required.¹¹ Therefore, it is possible that the risk of JAK inhibitor induced teratogenicity is mitigated with initiation beyond the first trimester. More evidence is required to understand the safety of JAK inhibitors during pregnancy and optimal timing of exposure.

There is similarly limited data on the use of upadacitinib in breastfeeding. While tofacitinib passes through breastmilk, the infant dose appears at most 3.4% of the maternal dose, which is below the accepted value of 10%.⁸ Pharmacodynamic data from animal studies suggest upadacitinib is present in breastmilk; thus, breastfeeding while taking upadacitinib is not recommended due to unknown effects.¹

Pregnant patients have an increased risk of adverse perinatal outcomes when their inflammatory bowel disease is active.^12,13 This patient had obstetrically uncomplicated pregnancies despite UC flares during 3 of her 4 pregnancies. The impact of prompt, effective treatment with upadacitinib and access to multidisciplinary care likely contributed to this patient's good outcomes.

There are some limitations to this case. Oligohydramnios was an adverse event, though it is unclear to what extent upadacitinib, maternal disease activity, or preexisting obstetric factors contributed to this outcome. Similarly, she received corticosteroids before upadacitinib. Though she was not improving before upadacitinib, it is possible that corticosteroid use contributed to clinical and biochemical improvement. Finally, maternal or neonatal blood sampling to assess drug levels would be useful, as done in a prior case series.⁴

Additional research is needed to evaluate pregnancy and neonatal outcomes with upadacitinib, as the contraindication designation may be inappropriate, particularly if initiated beyond the first trimester. An unfavorable pregnancy risk categorization may limit remission for pregnant individuals with refractory inflammatory bowel disease (IBD), since many clinicians and patients may defer use.

DISCLOSURES

Author contributions: LG Rabinowitz, JD Feuerstein, MJ Wanf, M. Spiel: conceptualization, editing the manuscript, and is the article guarantor; G. Geeganage: literature review, drafting the manuscript; DJ Flynn: drafting the manuscript, literature review; S. Martinez: drafting the manuscript, editing the manuscript.

Financial disclosure: None to report.

Informed consent was obtained for this case report.