Thiopurine therapy, commonly used in autoimmune conditions, can be complicated by life-threatening leukopenia. This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent. Here we performed an Immunochip-based 2-stage association study in 978 Korean subjects with Crohn’s disease treated with thiopurines. We identified a nonsynonymous SNP in NUDT15 (encoding p.Arg139Cys) that was strongly associated with thiopurine-induced early leukopenia (odds ratio (OR) = 35.6; Pcombined = 4.88 × 10−94). In Koreans, this variant demonstrated sensitivity and specificity of 89.4% and 93.2%, respectively, for thiopurine-induced early leukopenia (in comparison to 12.1% and 97.6% for TPMT variants). Although rare, this SNP was also strongly associated with thiopurine-induced leukopenia in subjects with inflammatory bowel disease of European descent (OR = 9.50; P = 4.64 × 10−4). Thus, NUDT15 is a pharmacogenetic determinant for thiopurine-induced leukopenia in diverse populations.

Korean CD patients differed from Western patients in gender distribution, disease location, and perianal fistula occurrence. Korean CD patients may also have better clinical courses than Western patients, as indicated by the lower intestinal resection rate.

BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore 2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/ W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (C trough,W22 ), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for C trough,W22 of 1154.17% (90% CI 786.37-1694.00; n ¼ 59 [CT-P13 SC]; n ¼ 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy,

Background and Aims Although the incidence of inflammatory bowel disease [IBD] is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal trends in the epidemiology of Crohn’s disease [CD] and ulcerative colitis [UC] in Seoul, Korea. Methods This population-based study included 1431 IBD patients [418 CD, 1013 UC] diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed. Results The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval [CI], 0.05–0.07) and 0.29 [95% CI, 0.27–0.31], respectively, in 1986–1990 to 2.44 [95% CI, 2.38–2.50] and 5.82 [95% CI, 5.73–5.92], respectively, in 2011–2015. Average annual percentage change in IBD incidence was 12.3% in 1986–1995, 12.3% in 1996–2005, and 3.3% in 2006–2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 [95% CI, 31.10–32.07] for CD and 76.66/100 000 [95% CI, 75.91–77.42] for UC. Conclusions The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.

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Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.

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