An early intervention with IFX monotherapy should prevent clinical, serological, and endoscopic CD recurrence following ileocolic resection. Thiopurine naivety and eliminating the initial loading dose of IFX might minimize serious AEs.
Background/AimsRecent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).MethodsOne hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.ResultsNone of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.ConclusionsOf the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
Low-CD25(High+)CD4(+), a subset of regulatory CD25(+)CD4(+) T cells and high-inflammatory CD28(-)CD4(+) T cells can exacerbate ulcerative colitis (UC). This study sought to investigate the frequency of CD25(High+)CD4(+) and CD28(-)CD4(+) T cells in patients with UC and the changes in these cells during Adacolumn granulocyte and monocyte adsorption apheresis (GMA). Subjects were 12 patients with active UC, 11 with quiescent UC, and 14 healthy volunteers (HVs). The mean clinical activity index was 15.7 +/- 2.2 in active UC and 4.5 +/- 1.1 in quiescent UC. Peripheral blood samples were stained with CD4, CD25, and CD28 antibodies for flow cytometry. Patients with active UC received GMA and blood samples were examined before and after the first GMA session. Patients with active UC (P < 0.04) or quiescent UC (P < 0.02) had a higher percentage of CD28(-)D4(+)T cells compared with HVs, while the percentage of CD28(+)CD4(+) T cells was lower in both UC groups compared with HVs (P = 0.03 and P < 0.02). Patients with active UC had a lower percentage of CD25(High+)CD4(+)T cells compared with quiescent UC patients (P < 0.001). A significant increase in CD25(High+)CD4(+) T cells was associated with GMA (P < 0.03). Low CD25(High+)CD4(+) and high CD28(-)CD4(+) are prominent features in UC. The increase in CD25(High+)CD4(+) T cells induced by GMA should contribute to improved immune function. Additional studies are warranted, since a low frequency of CD25(High+)CD4(+) (-) and a high frequency of CD28(-)CD4(+) (-) expressing T cells might be a predictor of clinical response to GMA.
BackgroundAdsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients’ demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC.MethodsIn a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger’s clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients’ demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied.ResultsAfter 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032).ConclusionsIn this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.
<b><i>Introduction:</i></b> Ustekinumab (UST) is an antibody to the p40 subunit of interleukins 12 and 23 in Crohn’s disease (CD) patients. Few reports are available on CD in the Asian scenario. <b><i>Objective:</i></b> We evaluated UST’s efficacy in inducing remission and its maintenance in Japanese CD patients. <b><i>Methods:</i></b> This retrospective study was conducted in UST-treated CD patients at our center. The primary endpoint was the clinical remission rate at week 8; the major secondary endpoints were the clinical remission rate at week 24 or 48, change in CD activity index (CDAI) and biomarkers, endoscopic efficacy, and cumulative remission maintenance rate. <b><i>Results:</i></b> The clinical remission rates at weeks 8, 24, and 48 were 44.4, 66.7, and 50.0%, respectively. Delayed response was shown by 22.2% of the patients; they achieved remission by week 24. The baseline CDAI was significantly lower in the remission group than in the nonremission group at week 8 (95% CI 0.89–0.99; <i>p</i> = 0.03). The cumulative remission maintenance rates at 6 and 12 months were 82.4 and 49.8%, respectively. Loss of response (LOR) was noted in 22.2% of the patients within 1 year. The endoscopic response and mucosal healing rate were 52.6 and 5.3%, respectively. Rapid improvements in serum albumin levels were observed at weeks 8 (<i>p</i> = 0.06), 24 (<i>p</i> < 0.01), and 48 (<i>p</i> = 0.01) from the baseline in active cases at baseline. <b><i>Conclusions:</i></b> UST is effective for remission induction and maintenance, especially in those with lower CD activity, however, may result in delayed response or LOR.
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