Efficacy of restarting anti-tumor necrosis factor α agents after surgery in patients with Crohn’s disease

Sakiko Hiraoka,Shiho Takashima,Yoshitaka Kondo,Toshihiro Inokuchi,Yuusaku Sugihara,Masahiro Takahara,Seiji Kawano,Keita Harada,Wakayama Medical University,Hiroyuki Okada 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: The efficacy of anti-tumor necrosis factor α (anti-TNFα) antibodies for postoperative Crohn’s disease(CD) in patients who were treated with these agents prior to surgery is largely unknown. Methods: CD patients who underwentintestinal resection and received anti-TNFα agents after surgery were divided into 2 groups according to the presence orabsence of preoperative anti-TNFα treatment: anti-TNFα restart group or anti-TNFα naïve group. Endoscopic recurrence aftersurgery was examined according to the preoperative conditions, including administration of anti-TNFα agents before surgery. Results: Thirty-six patients received anti-TNFα antibody after surgery: 22 in the anti-TNFα restart group and 14 in the anti-TNFα naïve group. Endoscopic recurrence after surgery was more frequently observed in the anti-TNFα restart group than inthe anti-TNFα naïve group (68% vs. 14% , P <0.001). Multivariate analysis revealed the following significant risk factors of endoscopicrecurrence after surgery: anti-TNF restart group (odds ratio [OR], 28.10; 95% CI, 3.08−722.00), age at diagnosis <23 years(OR, 24.30; 95% CI, 1.67−1,312.00), serum albumin concentration at surgery <3.3 g/dL (OR, 34.10; 95% CI, 1.72–2,804.00), andpresence of inflammation outside of the surgical site (OR, 21.40; 95% CI, 1.02−2,150.00). Treatment intensification for patientswith endoscopic recurrence in the anti-TNFα restart group showed limited responses, with only 1 of 12 patients achieving endoscopicremission. Conclusions: The efficacy of restarting anti-TNFα antibody treatment after surgery was limited, and treatmentintensification or a change to different classes of biologics should be considered for those patients.

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( Sakiko Hiraoka ),( Jun Kato ),( Hiroyuki Okada ) 대한장연구학회 2018 Intestinal Research Vol.16 No.2

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces

( Sakiko Hiraoka ),( Shiho Takashima ),( Toshihiro Inokuchi ),( Asuka Nakarai ),( Masahiro Takahara ),( Keita Harada ),( Yasuhiro Seki ),( Katsunori Watanabe ),( Jun Kato ),( Hiroyuki Okada ) 대한장연구학회 2019 Intestinal Research Vol.17 No.2

Background/Aims: Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. Methods: Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. Results: The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. Conclusions: The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC. (Intest Res 2019;17:202-209)

Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis

Sakiko Hiraoka,Toshihiro Inokuchi,Asuka Nakarai,Shiho Takashima,Daisuke Takei,Yuusaku Sugihara,Masahiro Takahara,Keita Harada,Hiroyuki Okada,Jun Kato 거트앤리버 소화기연관학회협의회 2018 Gut and Liver Vol.12 No.2

Background/Aims: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. Methods: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. Results: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p<0.0001 vs r=0.30, p=0.054). Conclusions: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin?

( Jun Kato ),( Sakiko Hiraoka ),( Asuka Nakarai ),( Shiho Takashima ),( Toshihiro Inokuchi ),( Masao Ichinose ) 대한장연구학회 2016 Intestinal Research Vol.14 No.1

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn’s disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted. (Intest Res 2016;14:5-14)

An Elevated Platelet Count Increases the Risk of Relapse in Ulcerative Colitis Patients with Mucosal Healing

( Asuka Nakarai ),( Jun Kato ),( Sakiko Hiraoka ),( Shiho Takashima ),( Toshihiro Inokuchi ),( Masahiro Takahara ),( Yuusaku Sugihara ),( Keita Harada ),( Hiroyuki Okada ) 대한소화기학회 2018 Gut and Liver Vol.12 No.4

Background/Aims: Although mucosal healing (MH) has been considered a treatment goal for patients with ulcerative colitis (UC), the risk factors predictive of relapse in patients who achieve MH are unknown. Because the platelet count has been shown to be a marker of inflammation in inflammatory bowel diseases, this study aimed to assess whether the platelet count could predict relapse in UC patients with MH. Methods: A prospective observational study was performed. UC patients with MH were consecutively enrolled in the study and monitored for at least 2 years or until relapse. The correlation between the incidence of relapse and the platelet count at the time of study enrollment was examined. Results: In total, 43 patients were enrolled, and 14 patients (33%) relapsed. The median platelet count at the time of enrollment in the patients who relapsed significantly differed from that in the patients who did not relapse (27.2×10⁴/μL vs 23.8×10⁴/μL, respectively; p=0.016). A platelet count >25.0×10⁴/μL was a significant risk factor for relapse based on a multivariate analysis (hazard ratio, 4.85; 95% confidence interval, 1.07 to 25.28), and according to the Kaplan-Meier analysis, this cutoff could identify patients susceptible to relapse (p=0.041, log-rank test). Conclusions: The platelet count could be used as a predictor of relapse in UC patients with MH. (Gut Liver 2018;12:420-425)