Korean Children and Adolescents with Crohn's Disease Are More Likely to Present with Perianal Fistulizing Disease at Diagnosis Compared to Their European Counterparts

Kang, Ben; Kim, Jung Eun; Jung, Jae Hun; Choe, Jae Young; Kim, Mi Jin; Choe, Yon Ho; Kim, Seung; Koh, Hong; Lee, Yoo Min; Lee, Jee Hyun; Lee, Yoon; Lee, Ji Hyuk; Lee, Hae Jeong; Jang, Hyo-Jeong; Choi, You Jin; Choi, So Yoon; Kim, Ju Young; Choe, Byung‐Ho

doi:10.5223/pghn.2020.23.1.49

Cited by 22 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 1 Approximately 25% of patients with IBD develop IBD-compatible symptoms before reaching the age of 20 years, and IBD in patients <20 years old typically exhibit a more aggressive phenotype than that seen in adults. 2 - 4 Early effective treatment is therefore crucial in pediatric IBD patients. 5 , 6 Likewise, treatment strategies in pediatric IBD have evolved to introduce anti-tumor necrosis factor (TNF) agents earlier in the disease course.…”

Section: Introductionmentioning

confidence: 99%

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background/Aims: Anti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients. Methods: Pediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this crosssectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors. Results: A total of 76 patients (Crohn's disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%). Conclusions: IFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.

show abstract

Section: Introductionmentioning

confidence: 99%

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial idiopathic chronic disease of the gastrointestinal tract 1 . Approximately 25% of patients with IBD are diagnosed at ages <20 years, and the incidence of IBD in paediatric populations has significantly increased during the past few decades 2‐5 . Paediatric‐onset IBD usually presents with a more severe phenotype compared to adult‐onset IBD, requiring earlier and more intensive treatment with immunomodulators and/or biologics 6,7 …”

Section: Introductionmentioning

confidence: 99%

Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers

Kang

Kim

Baek

et al. 2020

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

Background: The association between NUDT15 polymorphisms and thiopurine-induced leucopenia is well known. Aim: To investigate the association between NUDT15 polymorphisms and time-toleucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6-thioguanine nucleotide (6-TGN) levels. Methods: This retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time-to-leucopenia and the relationship between NUDT15 polymorphisms and 6-TGN levels were analysed. Results: Among the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolizers respectively (P < 0.001). NUDT15 polymorphism was significantly associated with time-to-leucopenia (HR = 5.26, 95% CI = 2.74-10.09, P < 0.001). There was a positive association between 6-TGN levels and leucopenia among the NUDT15 intermediate/TPMT normal metabolizers (median 361.3 vs 263.8 pmol/8 × 10 8 RBC, P = 0.013). The most accurate 6-TGN cutoff level associated with leucopenia was 308.2 pmol/8 × 10 8 RBC (AUC = 0.742, 95% CI = 0.569-0.915, sensitivity 80.0%, specificity 72.7%, P < 0.001) in this subgroup. When the specificity was set to <15%, the 6-TGN cutoff level was 167.1 pmol/8 × 10 8 RBC (sensitivity 93.3%, specificity 13.6%). Conclusions: NUDT15 polymorphisms were associated with time-to-leucopenia during azathioprine treatment in Korean paediatric patients with IBD. In order to reduce the development of thiopurine-induced leucopenia (<15%) in NUDT15 intermediate metabolizers, adjustment of azathioprine doses should be based on a lower 6-TGN target level (<167.1 pmol/8 × 10 8 RBC).

show abstract

“…Crohn’s disease (CD) is a chronic inflammatory bowel disease, which can affect the entire gastrointestinal (GI) tract [ 1 ]. Approximately 25% of patients with CD are diagnosed <20 years; moreover, the incidence of CD has notably increased in children [ 1 - 4 ]. Pediatric-onset CD is known to have a more aggressive disease course than that of adult-onset CD, requiring an early introduction of immunomodulators and/or anti-tumor necrosis factor (anti-TNF) agents [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Prevention of thiopurine-induced early leukopenia in a Korean pediatric patient with Crohn’s disease who turned out to possess homozygous mutations in NUDT15 R139C

Bae

Choe

Kang

2020

Yeungnam Univ J Med

Self Cite

View full text Add to dashboard Cite

Homozygous mutations in NUDT15 R139C are known as the major factor associated with thiopurine-induced early leukopenia, particularly in Asian patients. Therefore, NUDT15 genotyping is currently recommended before thiopurine treatment to identify patients who are NUDT15 poor metabolizers and consider the use of an alternative immunomodulatory therapy. We report a case of a 12-year-old Korean girl with Crohn’s disease (CD), in whom thiopurine-induced leukopenia was prevented by initiation of azathioprine (AZA) therapy at a low dose (0.5 mg/kg/day) and early detection of significant hair loss and white blood cell (WBC) count decrease at 17 days from the start of AZA treatment. The WBC count dropped from 8,970/μL to 3,370/μL in 2 weeks, and AZA treatment was stopped because of concerns of potential leukopenia in the near future. Her WBC count recovered to 5,120/μL after 3 weeks. Gene analysis later revealed that she had a homozygous mutation in NUDT15 R139C, resulting in a poor metabolizing activity of NUDT15. In situations when NUDT15 genotyping is unavailable, initiation of AZA therapy at 0.5 mg/kg/day with close observation of hair loss and WBC counts within 2 weeks may be an alternative way to prevent thiopurine-induced early leukopenia in Asian children with CD.

show abstract

Korean Children and Adolescents with Crohn's Disease Are More Likely to Present with Perianal Fistulizing Disease at Diagnosis Compared to Their European Counterparts

Cited by 22 publications

References 41 publications

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers

Prevention of thiopurine-induced early leukopenia in a Korean pediatric patient with Crohn’s disease who turned out to possess homozygous mutations in NUDT15 R139C

Contact Info

Product

Resources

About