Clinical Case Summary

An 18-year-old female was diagnosed with very early-onset Crohn’s disease (CD) in 2008. Due to steroid dependence, adalimumab 40 mg biweekly was initiated in 2019, with escalation to 40 mg weekly in February 2023 following secondary loss of response. In November 2023, despite clinical and biochemical remission (CRP <0.5 mg/L, fecal calprotectin <50 µg/g), the patient developed painful purpuric and ulcerated lesions on both lower limbs. Histological examination of a skin biopsy confirmed leukocytoclastic vasculitis (LCV), revealing perivascular neutrophilic infiltrates, nuclear debris, and fibrinoid necrosis in post-capillary venules. Infectious and autoimmune screening, including ANA, antiphospholipid antibodies, p-ANCA, and c-ANCA, were negative. Following consultation with an immunologist, adalimumab was discontinued, and oral prednisone 25 mg/day was initiated. However, the clinical course was complicated by a skin abscess, which was treated with oral amoxicillin/clavulanate (1 g three times daily for 3 days). As vasculitic lesions worsened, the patient was hospitalized, and prednisone was increased to 50 mg/day. Intravenous cefazolin (2 g every 8 hours for 5 days) was also administered, resulting in stabilization and partial clinical improvement. A multidisciplinary team, including a gastroenterologist, immunologist, and dermatologist, opted to initiate off-label treatment with upadacitinib 30 mg/day, a selective Janus kinase 1 (JAK1) inhibitor. After four weeks, the patient showed improvement in the vasculitic lesions, and corticosteroid therapy was tapered. At the six-month follow-up, the patient remained on upadacitinib monotherapy, with sustained clinical and biochemical remission of both CD and LCV, without any adverse events. This case highlights the potential of JAK1 inhibition as an effective and safe therapeutic option for leukocytoclastic vasculitis in patients with Crohn’s disease.

References

Photographic documentation of the clinical case:
1. Images showing the initial presentation of petechial and purpuric lesions on the lower limbs.
2. Images of severe vasculitis characterized by confluent and ulcerated lesions.
3. Images documenting cutaneous healing following upadacitinib treatment.

Introduction

Secondary loss of response to Infliximab(IFX) occurs in approximately half of patients with Inflammatory Bowel Disease(IBD), due to drug levels falling below the therapeutic range. This study evaluated IFX levels and related clinical and laboratory parameters and their impact on clinical outcomes.

Aims & Methods

Pre-infusion drug levels, associated laboratory data, and clinical parameters were evaluated in IBD patients receiving maintenance doses of IFX(5–15 mg/kg every 4–8 weeks) between Nov2021-Apr2025. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4–20µg/mL.

Results

A total of 1,059 single pre-infusion measurements from 455 patients and consecutive dual measurements at weeks 4 and 8 from 64 patients were evaluated. In the single and double measurement groups, 75.4% and 84.4% of patients had Crohn’s disease(CD), respectively. The most commonly used doses were 5 mg/8 weeks and 10 mg/4 weeks(Table 1) Drug levels were below 5 µg/mL in 33% of the measurements. Antibody positivity was present in 47.5% of 120 available measurements ranging from 0.4-20 µg/mL, showing no significant correlation with drug levels or immunomodulatory(IM) use (p=0.62 and p=0.61) However, for all positive antibody measurements drug levels were ≤ 3.5 µg/mL. CRP differed significantly across drug level groups, whereas albumin did not(Table 1). A weak negative correlation was found between IFX levels and CRP(r = -0.13, p = 0.001), with no correlation for albumin(p=0.54). In UC patients, the correlation between CRP and IFX levels was slightly stronger(r= -0.280, p=0.004).No significant associations were found between IM use and IFX levels >5 µg/mL(p=0.55), >10 µg/mL(p= 0.93), or >20µg/mL(p = 0.87). Abdominal pain was more common in patients with IFX levels <5 µg/mL (p=0.032) and <10 µg/mL (p=0.044). Smoking status was not associated with achieving IFX levels >5 µg/mL( p=0.57), >10 µg/mL (p=0.89), and >20 µg/mL (p=0.633). Among CD patients, those with IFX levels >5 µg/mL had significantly lower CDAI scores (p = 0.039), and lower daily stool frequency (p=0.002).Regression analysis showed that higher BMI (p=0.045), lower CRP(p < 0.001), higher IFX dose(p < 0.001), and CD diagnosis(p =0.014) to be independently associated with achieving IFX levels >5 µg/mL. These factors also predicted levels >10 µg/mL and >20 µg/mL, except for BMI at the >20 µg/mL threshold. In the dual measurement group, the median CRP levels at weeks 4 and 8 were 2.1(5.1) and 2.5(6.3), respectively (p = 0.108). Among patients with IFX >20 µg/mL at week 4, 75% maintained levels >5 µg/mL at week 8, whereas this rate was 64% for those with levels >10 µg/mL. Only 59.6% of those with >5 µg/mL at week 4 retained >5 µg/mL at week 8(all p <0.001). Week 4 IFX levels was 7.3 times higher than at week 8 for cases within measurable range.

Conclusion

One-third of patients demonstrated sub-therapeutic drug levels, which were associated with elevated CRP levels and worse clinical outcomes. Notably, the 5mg/4 weeks group exhibited higher drug concentrations compared to the 10mg/8 weeks group, suggesting that increased infusion frequency may contribute to achieving higher levels. Moreover, maintaining sufficient drug levels at week 8 requires substantially higher levels at week 4. Measurement of anti-TNF antibodies may not be fruitful if drug level is > 3.5µg/mL. These findings support the drug monitoring and personalized dosing to reduce the risk of loss of response and improve outcomes.

Introduction

Difficult-to-treat Crohn’s disease (CD), as defined by the International Organization for the Study of IBD (IOIBD), encompasses patients with persistent disease activity despite advanced therapies, complex phenotypes (e.g., penetrating complications), or post-surgical recurrence. Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy in Western populations, yet data in Asian cohorts remain sparse. This study evaluates the effectiveness and safety of standardized induction regimen of upadacitinib (45mg qd) in Asian patients meeting IOIBD criteria for difficult-to-treat CD.

Aims & Methods

To assess the efficacy and safety of upadacitinib in Asian patients with difficult-to-treat CD, providing evidence for clinical decision-making, a retrospective, multicenter study was conducted from 8 Chinese tertiary centers (January 2023–January 2025) on difficult-to-treat Crohn’s disease patients who met IOIBD criteria. All patients received upadacitinib 45mg qd for 12 weeks. Clinical outcomes were assessed using the Crohn's Disease Activity Index (CDAI), with the primary outcome being clinical remission (CDAI <150) and the secondary outcome being clinical response (CDAI reduction ≥70) at week 12. Adverse events (AEs) were systematically recorded.

Results

We finally collected 151 patients who met IOIBD criteria(Table1). Among them, 147 patients presented failure of ≥2 biologics with distinct mechanisms, 3 patients had complex perianal disease and 1 patient had postoperative recurrence. The mean disease duration of these patients was 7.6 years (SD 4.5 years). At week 12, 71 patients (47.0%) achieved clinical remission, 66 patients (43.7%) showed clinical response, and 14 patients (9.3%) were non-responders. Adverse events occurred in 40 patients (26.5%): acne (n=13), anemia (n=13), leukopenia (n=3), fever (n=4), urinary tract infection (n=2), herpes zoster (n=2), folliculitis (n=1), amenorrhea (n=1), elevated creatine phosphokinase (n=1), and mediastinal tuberculosis (n=1). Most AEs were mild and resolved with oral medications.

Table1. Baseline Characteristics of Patients with Difficult-to-Treat CD Treated with UPA

Conclusion

This is the largest Asian cohort study of upadacitinib for difficult-to-treat CD. The drug demonstrated robust efficacy and a favorable safety profile. Notably, tuberculosis reactivation was rare. Standard dosing showed comparable effectiveness and tolerability to European data, underscoring upadacitinib as a strong therapeutic option in Asian populations.

References

1. Parigi TL, D'Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1
2. Parigi TL, Massimino L, Carini A, et al. Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease. J Crohns Colitis. 2025;19(3):jjae145. doi:10.1093/ecco-jcc/jjae145
3. Bezzio C, Franchellucci G, Savarino EV, et al. Upadacitinib in Patients With Difficult-to-Treat Crohn's Disease [published correction appears in Crohns Colitis 360. 2025 Mar 25;7(1):otaf022. doi: 10.1093/crocol/otaf022.]. Crohns Colitis 360. 2024;6(4):otae060. Published 2024 Oct 24. doi:10.1093/crocol/otae060
4. Devi J, Xu A, Stone M, et al. Real-World Effectiveness and Safety of Upadacitinib in Crohn's Disease: A Multicenter Study. Clin Gastroenterol Hepatol. Published online March 8, 2025. doi:10.1016/j.cgh.2025.01.012

Clinical Case Summary

Introduction: Eosinophilic enteritis (EoEo) is a rare condition characterized by eosinophilic infiltration of the intestinal wall without an identifiable secondary cause. Clinical presentation varies depending on the affected intestinal segment and layer. While mucosal involvement causes digestive symptoms, muscular involvement may lead to obstruction, and serosal involvement—least common—can present with eosinophilic ascites.
Case Report: A 15-year-old male presented with epigastric pain, vomiting, and oral intolerance. Laboratory tests revealed marked eosinophilia (>5,000/μL). Abdominal CT showed free fluid and ileocecal wall thickening. Diagnostic paracentesis revealed ascitic fluid with a high leukocyte count and eosinophil predominance. Endoscopic studies revealed ileitis, typhlitis, and duodenitis. Biopsies confirmed eosinophilic infiltration of the intestinal wall. Other causes of eosinophilia, including infections and malignancy, were ruled out. The patient was treated with intravenous corticosteroids, with good clinical response, and discharged on oral budesonide. A relapse occurred after tapering steroids, prompting initiation of azathioprine for maintenance. The patient remains clinically stable without further hospitalizations.
Discussion: EoEo with eosinophilic ascites is rare and should be considered in the differential diagnosis of unexplained ascites, particularly in patients with peripheral eosinophilia. Key diagnostic findings include eosinophil-predominant ascitic fluid and GI tract biopsies with eosinophilic infiltration. Early recognition and treatment are essential to prevent complications. It is crucial to rule out parasitic and infectious causes before initiating corticosteroid therapy to avoid worsening an undiagnosed infection.