Introduction

JAK inhibitors (JAKi) are small molecules capable of crossing the placenta via passive diffusion or active extracellular transport from early pregnancy.¹ Data on the risks of in utero JAKi exposure are limited,² particularly regarding pregnancy outcomes, infant infections, vaccine responses, and childhood development.

Aims & Methods

We conducted a multicenter retrospective JAKi and pregnancy observational study supported by the ECCO Collaborative Network for Exceptionally Rare Case Reports (CONFER). Pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO) during pregnancy were enrolled from 21 centers across 15 countries. Data collected included maternal demographics, IBD characteristics, disease activity, medication use - including timing and duration of JAKi exposure - along with maternal, pregnancy, and infant outcomes.

Results

Of 43 JAKi exposed pregnancies, 17 (39.5%) were unplanned. Disease activity was present in 22 (51.2%) of the pregnancies. One-in-five women initiated JAKi in pregnancy (n=8, 18.6%). Abortion occurred in 8 cases, at a median gestational age (GA) of 8.5 weeks (range 3-16). Of these, 3 (7.0%) were spontaneous and 5 (11.6%) induced, with two terminations due to concerns about potential adverse effects of JAKi treatment. Of the remaining 35 pregnancies 26 (74.3%) were exposed to TOFA (5 mg BID (n=9), 10 mg BID (n=17)), 8 (22.9%) to UPA (30 mg daily (n=2), 45 mg daily (n=6)) and one (2.9%) to FILGO (200 mg daily). The majority received JAKi treatment throughout pregnancy (n=24, 68.6%). Discontinuation of JAKi during the 1^st or 2^nd trimester was followed by disease activity in 7 of 11 cases (63.6%). Maternal complication risk was low: no cases of DVT or (pre)eclampsia; premature rupture of membranes (GA 34–37) occurred in 3 cases, and 4 women required hospitalization due to infection or other complications. Among 35 live births, one infant (2.9%) was preterm (GA 34), three (8.6%) were small for gestational age, one (2.9%) had an Apgar score <7 at 5 minutes, and no congenital abnormalities were reported. Follow-up infant data are shown in table 1. One-third of breastfeeding women continued JAKi treatment. A high adherence rate to the national immunization schedule was seen. Three (8.6%) skipped the live rotavirus vaccine due to in uteroJAKi exposure. No adverse effects were reported following live attenuated or inactivated vaccines, and no malignancies were observed.

Conclusion

In this global multicenter study of JAKi exposure during pregnancy in women with IBD, maternal complication rates were low, and no increased risk of adverse pregnancy outcome were observed among live births. While disease activity was common, particularly following early discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to guide decision-making regarding the use of JAKi in pregnancy, though further prospective studies are needed to confirm long-term safety.

References

1. Fein KC, Arral ML, Kim JS, et al. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. J Control Release 2023;361:29-39.
2. Torres J, Chaparro M, Julsgaard M, et al. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1-27.

Disclosure

M. Julsgaard: Advisory board for AbbVie. G. Santana: Speaker and advisory board for pfizer.

Introduction

Although endoscopic balloon dilation (EBD) remains the standard intervention for Crohn’s disease (CD)-associated strictures, its efficacy is limited by high recurrence and surgery rates. Retrospective analyses suggest endoscopic stricturotomy (ES) may offer superior outcomes, particularly in anastomotic strictures. However, no randomized trials have directly compared EBD and ES for short CD-related strictures.

Aims & Methods

This single-center, randomized controlled trial (August 2022–March 2025) enrolled adult CD patients (18–65 years) with symptomatic, predominantly fibrotic or mixed, short strictures (<3 cm), including both de novo and anastomotic types, accessible via standard endoscopy. Patients with multiple (>2) strictures, strictures beyond endoscopic reach, or prior stricturotomy were excluded. Participants were randomized to undergo either EBD or ES. The primary outcome was clinical recurrence at 1 year. Secondary outcomes included re-intervention, surgery, emergency visits, hospitalization, technical success, and adverse events.

Results

Out of 70 randomized patients, 69 were analyzed (EBD: 35; ES: 34). Baseline characteristics were comparable between groups. Technical success was similar (EBD: 91.4%, ES: 94.1%). On time to event analysis, clinical recurrence was significantly lower in the ES group (OR=0.343, 95% CI: 0.134–0.881; p=0.026). Re-intervention rates favored ES (EBD: 25.7%, ES: 8.8%; OR=0.337, 95% CI: 0.131–0.870; p=0.025). Surgery rates were numerically lower with ES (EBD: 11.4%, ES: 5.9%) but not statistically significant (p=0.581). Hospitalization was significantly more frequent in the EBD arm (OR=0.276, 95% CI: 0.091–0.840; p=0.023). ED visits also trended lower with ES, though not statistically significant (p=0.062) (see table). Adverse events occurred in 25.7% of EBD patients (bleeding n=3 [1 hemoclip], pain with admission n=3, micro-perforation n=1, post-procedure pain n=2) and 14.7% of ES patients (bleeding n=3 [1 self-limited, 1 coagrasper, 1 hemoclip], none required transfusion, suspected perforation n=1, mild pain n=1).

Conclusion

In this interim analysis, ES was associated with significantly lower clinical recurrence, re-intervention, and hospitalization compared to EBD for short CD-related strictures, with similar safety outcomes. These findings support ES as a potentially superior first-line endoscopic strategy over EBD in selected patients with Crohn’s disease strictures. (NCT05521867)

References

Lan N, Shen B. Endoscopic Stricturotomy Versus Balloon Dilation in the Treatment of Anastomotic Strictures in Crohn's Disease. Inflamm Bowel Dis. 2018 Mar 19;24(4):897-907. doi: 10.1093/ibd/izx085. PMID: 29546384.

Introduction

Side effects, patient preference, and high costs may prompt cessation of anti-TNF therapy in ulcerative colitis (UC) patients in sustained remission. Given the risk of relapse, careful patient selection is essential. This study aimed to assess relapse rates and identify predictors of relapse following anti-TNF cessation in UC patients in remission.

Aims & Methods

A systematic search on cohort studies reporting relapse rates after cessation of anti-TNF therapy in ≥30 UC patients in clinical remission was performed 6 September 2024. Individual patient data was requested. We excluded patients with steroid use, ≤6 months anti-TNF therapy, ≤16 years, previous colectomy (n=4), golimumab as anti-TNF therapy (n=3) or without follow-up. Continuation of treatment with immunomodulators or mesalamine at cessation of anti-TNF was allowed. Relapse was defined as the need to (re)start treatment with steroids, anti-TNF or other advanced therapies, or the need for surgical treatment, as applied by the original author. Pooled relapse rates were computed using a random-effects model. A prediction model was built with a Cox proportional hazards model, performance assessed by iteratively leaving one study out (internal-external cross-validation, IECV). Missing covariate data were multiply imputed 100 times using the MICE algorithm. Variable selection was guided by three criteria: ≤20% missing data, a univariate p-value ≤ 0.2, and input from clinical experts.

Results

In total, 654 patients from 8 studies were included in the individual participant data meta-analysis. At anti-TNF cessation, median age was 40 years (IQR 31-51) with a median anti-TNF treatment of 18 months (IQR 18-36). The majority of patients were treated with infliximab (n = 610, 93%). Only 42 patients (9%) received a second-line anti-TNF therapy. The pooled relapse rate were 24% [95% CI 19-29%, I² = 44%] and 34% [95% CI 29-40%, I² = 39] at 1 and 2 years after cessation, respectively. Upon cessation, 211 patients (33%) continued mesalamine, 239 (39%) thiopurines, and 136 (22%) a combination of both. In our model, thiopurine therapy and older age at cessation were associated with a reduced risk of relapse, whereas immunomodulator refractoriness as an indication for starting anti-TNF therapy was associated with an increased risk. Other factors included in the prediction model were disease extent, type of anti-TNF therapy, history of anti-TNF therapy, fecal calprotectin level and endoscopic activity, leading to a c statistic of 0.55 [95% CI 0.51-0.59] (Table 1).

Table 1: Predictors of relapse in a pooled Cox regression analysis

Conclusion

Approximately 1 in 4 patients experience a relapse of UC within 1 year after anti-TNF cessation, increasing to 1 in 3 within 2 years. Continuation of thiopurines is associated with a reduced risk. A prediction model for relapse was developed in this large IPD meta-analysis cohort and may aid in shared decision-making on anti-TNF cessation. However, its limited discriminative ability underscores the need for further refinement, incorporating data on microscopic remission and molecular and immunological markers to better capture deeper disease control.