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STUDY AIMS The PillCam patency capsule (PPC) is an Agile tag-less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention. METHODS This prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively. RESULTS Of 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn's disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non-confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels

Background/aims An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease. Methods Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018. Results Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn's disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naive patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naive patient group. Conclusions In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease.

Background/Aims: Inhibition of α4β7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4β7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. Methods: In this randomized, double-blind, placebo-controlled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks. The double-blind period was followed by a 36-week open-label period, in which all patients received abrilumab 210 mg SC every 12 weeks, and a 28-week safety follow-up period. The primary efficacy variable was clinical remission at week 8 (total Mayo score ≤2 points with no individual subscore >1 point). Results: Clinical remission at week 8 was 4 out of 31 (12.9%) overall in the abrilumab groups versus 0 out of 13 in the placebo group (abrilumab 21 mg, 1/10 [10.0%]; 70 mg, 2/12 [16.7%]; 210 mg, 1/9 [11.1%]). In both the double-blind and open-label periods, fewer patients in the abrilumab groups experienced ≥1 adverse event compared with those in the placebo group. There were no cases of progressive multifocal leukoencephalopathy and no deaths. Conclusions: Abrilumab 70 mg and 210 mg yielded numerically better results in terms of clinical remission rate at Week 8 than placebo, with the 210 mg dose showing more consistent treatment effects. Abrilumab was well tolerated in Japanese patients with UC. (Intest Res 2019;17:375-386)

Administering double doses of infliximab or shortening its dosing interval for patients with Crohn disease who experience a loss of response to treatment is an accepted treatment method; however, the effectiveness and appropriate timing of treatment intensification remain unclear. We examined the treatment outcomes of patients with Crohn disease receiving infliximab therapy intensification.Among 430 patients with Crohn disease who were seen at our related facilities from July 2002 to July 2018, 46 patients (30 men and 16 women) who were followed up for diminished infliximab effects for >1 year after therapy intensification were included in this study. The relationship between patient background and continuation of therapy intensification was retrospectively examined through a logistic regression analysis.Among the 46 patients, 67.4% (31 cases) continued therapy intensification for 12 months. The treatment discontinuation rate after 12 months (7.1% vs 43.8%, P = .015) and the C-reactive protein levels at the start of therapy intensification (P = .0050) were significantly lower in the group in which treatment was strengthened due to remaining endoscopic findings (n = 14) than that due to clinical symptoms (n = 32). There was no significant difference in the rates of treatment discontinuation after 12 months of treatment strengthening between patients receiving double doses (n = 34) and those with shortened dosing intervals (n = 12).Infliximab treatment discontinuation seems to be less likely to occur in patients with Crohn disease who are receiving infliximab treatment intensification based on endoscopic findings of exacerbations than in patients whose treatment is based on clinical symptoms.

Background and aims: Carbohydrate sulfotransferase 15 (CHST15) is a specific enzyme biosynthesizing chondroitin sulfate E that binds various pathogenic mediators and is known to create local fibrotic lesions. We evaluated the safety of STNM01, a synthetic double stranded RNA oligonucleotide directed against CHST15, in Crohn’s disease (CD) patients whose mucosal lesions were refractory to conventional therapy. Methods: This was a randomized, double-blind, placebo-controlled, concentration-escalation study of STNM01 by a single dose endoscopic submucosal injection in 18 CD patients. Cohorts of increasing concentration of STNM01 were enrolled sequentially as 2.5 nM (n=3), 25 nM (n=3) and 250 nM (n=3) were applied. A cohort of placebo (n=3) was included in each concentration. Safety was monitored for 30 days. Pharmacokinetics was monitored for 24 hours. The changes from baseline in the segmental Simple Endoscopic Score for CD (SES-CD) as well as the histological fibrosis score were evaluated. Results: STNM01 was well-tolerated and showed no drug-related adverse effects in any cohort of treated patients. There were no detectable plasma concentrations of STNM01 at all measured time points in all treatment groups. Seven of 9 subjects who received STNM01 showed reduction in segmental SES-CD at day 30, when compared with those who received placebo. Histological analyses of biopsy specimens revealed that STNM01 reduced the extent of fibrosis. Conclusion: Local application of STNM01 is safe an well-tolerated in CD patients with active mucosal lesions. Clinical trial Registration (Investigational Medical Product) Number (Japan): 23-1655

A microenzyme-linked immunosorbent assay system employing monoclonal antibody SNH3 was developed for the detection of sialosyl Lewisx antigen in stool extracts from 80 patients with colorectal cancer, 13 patients with colorectal non-malignant disorders and 90 normal subjects. Sialosyl Lewisx antigen was detected in 35% of stool extracts from cancer patients but only in 7.7% and 2.2% of those from non-malignant patients and normal subjects respectively. Hemoglobin in the same stool samples was detected in 37.5% of cancer patients, 15.4% of non-malignant patients and 5.6% of normal subjects. The appearance of sialosyl Lewisx antigen in stool was not necessary correlated with that of hemoglobin, and overall 61.3% of cancer patients were detected by the combination of the two assays. The combination assay was also impressive in early detection of colorectal cancer (Dukes' A, 52%; Dukes' B, 57.1%). Therefore, the assay for sialosyl Lewisx antigen in stool would be useful for detecting colorectal cancer.

The tumor marker CA 19-9 was shown to be elevated in liver transplant patients, particularly during rejection. Serial serum samples taken from 24 patients after liver transplantation were examined for tumor markers CA 19-9, SLEX, CEA, and TNF-alpha. During rejection, 85% of the patients had elevated levels of CA 19-9. Patients with early rejection had persistently higher levels than patients without rejection. The serum levels were low in nonrejecting patients compared with those with rejection. Thus, the CA 19-9 marker cannot be considered a specific tumor marker. It may, however, be an indicator of an immune response or it may be a byproduct of an inflammatory reaction to a tumor or a transplant.