Masakazu Takazoe

Publications (32)117.47 Total impact

• Article: C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn's disease.

  Toshifumi Hibi, Atsushi Sakuraba, Mamoru Watanabe, Satoshi Motoya, Hiroaki Ito, Noriko Sato, Toru Yoshinari, Kenta Motegi, Yoshitaka Kinouchi, Masakazu Takazoe, Yasuo Suzuki, Takayuki Matsumoto, Kazuhiko Kawakami, Ichiro Hirata, Shinji Tanaka, Toshifumi Ashida, Toshiyuki Matsui
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: The ability of serum infliximab level to predict clinical outcome in infliximab therapy in Crohn's disease is unclear. Here, we aimed to clarify the correlation between the timing of loss of response (LOR) to treatment and a decrease in serum infliximab level, and, in addition, to identify an indicator of infliximab level. METHODS: The study used data from a previous clinical study of infliximab for Crohn's disease, in which infliximab was initially given at 0, 2, 6 weeks at 5 mg/kg, and then at 8-week intervals to 62 week-10 responders. Of these 62, here we analysed data from 57 in whom Crohn's disease activity index and serum infliximab level were evaluated at week 14. RESULTS: Twelve patients showed a clinical response despite an infliximab level <1 μg/mL at week 14; of these, 8 (67 %) experienced LOR by week 54. A decrease in infliximab level preceded LOR in 6 (75 %). In receiver operating characteristic curve analysis, C-reactive protein (CRP) showed better performance in detecting an infliximab level <1 μg/mL. Infliximab level was <1 μg/mL in 60-80 % of patients with CRP >0.5 mg/dL. Time to LOR (median: 22.0 weeks) was significantly longer than that to a decrease in infliximab level to <1 μg/mL (14.0 weeks, p < 0.05) or to an increase in CRP to >0.5 mg/dL (14.0 weeks, p < 0.01). CONCLUSIONS: A decrease in serum infliximab level preceded LOR, and was easily detected by an increase in CRP. The CRP may be an indicator of serum infliximab level in predicting LOR.
  Journal of Gastroenterology 04/2013; · 4.16 Impact Factor
• Article: Association Study of 71 European Crohn's Disease Susceptibility Loci in a Japanese Population.

  Atsushi Hirano, Keiko Yamazaki, Junji Umeno, Kyota Ashikawa, Masayuki Aoki, Takayuki Matsumoto, Shotaro Nakamura, Toshiharu Ninomiya, Toshiyuki Matsui, Fumihito Hirai, Takaaki Kawaguchi, Masakazu Takazoe, Hiroki Tanaka, Satoshi Motoya, Yutaka Kiyohara, Takanari Kitazono, Yusuke Nakamura, Naoyuki Kamatani, Michiaki Kubo
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  ABSTRACT: BACKGROUND:: A large-scale meta-analysis of a series of European genome-wide association studies revealed 71 susceptibility loci for Crohn's disease (CD). However, it is not clear whether these susceptibility loci are also shared with Japanese populations. METHODS:: We genotyped 71 single-nucleotide polymorphisms (SNPs) comprising 1311 CD cases and 6585 controls of Japanese descent, and their associations with CD were evaluated using the Cochran-Armitage trend test. In addition, genotype-phenotype analyses were conducted on the SNPs showing associations with Japanese CD based on the Montreal classification. RESULTS:: Twenty-seven SNPs showed at least nominal association (P < 0.05) and 11 of them remained significant even after Bonferroni correction (P < 0.0007). Despite high statistical power, we could not find any association in 17 loci. Moreover, SNPs in 9 loci were rare or absent in the Japanese population. Genetic variations involved in the innate immune system (NOD2, ATG16L1, and IRGM) showed no association with CD susceptibility in the Japanese population. Genotype-phenotype analyses showed that rs3810936, a marker of TNFSF15, correlated with severe CD phenotypes. CONCLUSIONS:: Our study suggests that there is a differential genetic background of CD susceptibility between Japanese and European populations.
  Inflammatory Bowel Diseases 02/2013; · 4.86 Impact Factor
• Article: A Genome-Wide Association Study Identifies 2 Susceptibility Loci for Crohn's Disease in a Japanese Population.

  Keiko Yamazaki, Junji Umeno, Atsushi Takahashi, Atsushi Hirano, Todd Andrew Johnson, Natsuhiko Kumasaka, Takashi Morizono, Naoya Hosono, Takaaki Kawaguchi, Masakazu Takazoe, [......], Masayo Hosokawa, Yoshiaki Arimura, Yasuhisa Shinomura, Toshiyuki Matsui, Takayuki Matsumoto, Mitsuo Iida, Tatsuhiko Tsunoda, Yusuke Nakamura, Naoyuki Kamatani, Michiaki Kubo
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  ABSTRACT: BACKGROUND & AIMS: Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population. METHODS: We performed a genome-wide association study with 372 individuals with Crohn's disease (cases) and 3389 controls, all from the Japanese population. To confirm identified associations, we performed a replication study with an independent panel of 1151 Crohn's disease cases and 15,800 controls. We also performed an association analysis using genome-wide genotype imputation in the discovery cohort. RESULTS: We confirmed associations of Crohn's disease with variants inMHC (rs7765379,P = 2.11 x 10(-59)),TNFSF15 (rs6478106,P = 3.87 x 10(-45)), andSTAT3 (rs9891119,P = 2.24 x 10(-14)). We identified 2 new susceptibility loci, on chromosome 4p14 (rs1487630,P = 2.40 x 10(-11), odds ratio = 1.33) and in theSLC25A15-ELF1-WBP4region on 13q14 (rs7329174 in ELF1,P = 5.12 x 10(-9), odds ratio = 1.27). CONCLUSIONS: In a genome-wide association study, we identified 2 new susceptibility loci for Crohn's disease in a Japanese population. These findings could increase our understanding of the pathogenesis of Crohn's disease.
  Gastroenterology 12/2012; · 11.68 Impact Factor
• Article: Incidence and characteristics of the 2009 influenza (H1N1) infections in inflammatory bowel disease patients.

  Makoto Naganuma, Toshimitsu Fujii, Reiko Kunisaki, Naoki Yoshimura, Masakazu Takazoe, Yoshiaki Takeuchi, Eiko Saito, Masakazu Nagahori, Keiko Asakura, Toru Takebayashi, Mamoru Watanabe
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  ABSTRACT: BACKGROUND: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009-2010. METHODS: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections. RESULTS: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20years was significantly higher than that among patients in other age groups (p<0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group. CONCLUSION: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed.
  Journal of Crohn s and Colitis 07/2012; · 2.57 Impact Factor
• Article: Efficacy and tolerability of oral budesonide in Japanese patients with active Crohn's disease: A multicentre, double-blind, randomized, parallel-group Phase II study.

  Yasuo Suzuki, Satoshi Motoya, Masakazu Takazoe, Tadashi Kosaka, Masataka Date, Masahiro Nii, Toshifumi Hibi
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  ABSTRACT: BACKGROUND AND AIMS: Current treatments for Japanese patients with active Crohn's disease have not proved optimal, and new treatment options are required. The present study therefore evaluated the efficacy and tolerability of oral budesonide in Japanese patients with mild-to-moderate active Crohn's disease. METHODS: In this multicentre, double-blind, randomized, parallel-group, Phase II study, patients (18-65years) with baseline Crohn's Disease Activity Index (CDAI) score≥200 were randomized to once-daily (od) oral budesonide 9mg or 15mg, or matching placebo, for 8weeks. Concomitant therapy with sulfasalazine or 5-aminosalicylic acid, and nutritional therapy, was allowed. The rate of remission (defined as CDAI score≤150) after 8weeks' treatment (primary variable), health-related quality of life (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability were assessed. RESULTS: 77 patients were randomized and 63 completed the study. The proportion of budesonide-treated patients with remission after 8weeks' treatment was higher compared with placebo (23.1%, 28.0%, and 11.5% for budesonide 9mg, 15mg, and placebo, respectively; no significant difference). The mean change from baseline to week 8 in CDAI total score (-48.0, -58.2, and -27.2, respectively) and IBDQ total score (10.8, 23.2, and 6.5, respectively) was greater for budesonide-treated patients than placebo recipients. While budesonide 9mg and 15mg demonstrated similar efficacy, budesonide 9mg caused fewer drug- and glucocorticosteroid-related adverse events and less adrenal suppression. CONCLUSIONS: Oral budesonide 9mg od (for up to 8weeks) may offer a new treatment option for Japanese patients with mild-to-moderate active Crohn's disease.
  Journal of Crohn s and Colitis 07/2012; · 2.57 Impact Factor
• Article: Sargramostim in patients with Crohn’s disease: results of a phase 1–2 study

  Masakazu Takazoe, Toshiyuki Matsui, Satoshi Motoya, Takayuki Matsumoto, Toshifumi Hibi, Mamoru Watanabe
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  ABSTRACT: BackgroundWe aimed to assess the tolerability, pharmacokinetics, safety, and efficacy of sargramostim in Japanese patients with active Crohn’s disease (CD). MethodsPatients with moderately to severely active CD were enrolled. Step 1 was an open-label, phase 1 study of 2μg/kg per day sargramostim administered subcutaneously (SC) for 4weeks, with an optional 8-week extension with 6μg/kg per day. Step 2 was an open-label, phase 1–2 study of the tolerability and pharmacokinetics of SC sargramostim 6μg/kg per day over 4weeks and of 8-week efficacy and safety. Efficacy variables were the proportion of patients achieving a clinical response [≥100-point decrease from baseline in the CD activity index (CDAI)] and the proportion achieving clinical remission (CDAI≤150 points). ResultsSix patients participated in Step 1; five in Step 2. Serum concentrations of sargramostim peaked within 1h of administration; mean terminal half-life was 2h. Maximal serum concentrations increased with the dose. Mean accumulation ratios were 0.998 in Step 1 and 0.673 in Step 2. One of the six patients in the Step-1 extension and none of the five in Step 2 achieved a clinical response. Clinical remission was reported in one patient in each step. A notable decrease in median CDAI scores was observed in the extension and Step 2. In responders, improvement tended to be maintained through the 30-day follow-up. Drug-related adverse events included injection-site reaction, pyrexia, back pain, and bone pain. ConclusionThe systemic exposure of sargramostim increased dose-dependently. No accumulation in systemic exposure was associated with the repeated once-daily administration. SC sargramostim at 6μg/kg per day improved median CDAI scores. A minority of patients experienced clinical remission or clinical response.
  Journal of Gastroenterology 04/2012; 44(6):535-543. · 4.16 Impact Factor
• Article: [Natural history and prognosis of inflammatory bowel diseases].

  Takaaki Kawaguchi, Masakazu Takazoe
  Nippon rinsho. Japanese journal of clinical medicine 02/2012; 70 Suppl 1:48-51.
• Article: Retrieval of serum infliximab level by shortening the maintenance infusion interval is correlated with clinical efficacy in Crohn's disease.

  Toshifumi Hibi, Atsushi Sakuraba, Mamoru Watanabe, Satoshi Motoya, Hiroaki Ito, Kenta Motegi, Yoshitaka Kinouchi, Masakazu Takazoe, Yasuo Suzuki, Takayuki Matsumoto, Kazuhiko Kawakami, Ichiro Hirata, Shinji Tanaka, Toshifumi Ashida, Toshiyuki Matsui
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  ABSTRACT: Infliximab has shown beneficial effects in the treatment of Crohn's disease (CD). The aim of this study was to assess 1) the clinical efficacy of shortening the infusion interval from 8 to 4 weeks when patients had shown loss of response during maintenance therapy, and 2) the association between the serum trough level and clinical efficacy. This was an open-label prospective multicenter study. Infliximab was administered at 5 mg/kg to patients with active CD at weeks 0, 2, and 6. Week 10 responders received infliximab every 8 weeks thereafter. In those with loss of response after week 14 the interval was switched to every 4 weeks. Co-primary endpoints were the rate of patients achieving clinical response and remission at week 54. Serum level of infliximab was measured at each visit. Fifty-seven patients who responded to induction treatment received maintenance therapy after week 14. Thirty-seven patients continued at the 8-week interval and 20 patients were switched to a 4-week interval. The overall clinical response and remission rates at week 54 were 82.5% and 61.4%, respectively. For those with loss of response, treatment at the 4-week interval resulted in clinical response and remission rates of 83.3% (15/18) and 55.6% (10/18), respectively, at week 54. A correlation between clinical efficacy and serum trough level was found (P < 0.01, overall). A treatment strategy with an option of shortening the dosing interval of infliximab retrieves its trough level and may be useful for maintaining its efficacy.
  Inflammatory Bowel Diseases 10/2011; 18(8):1480-7. · 4.86 Impact Factor
• Article: Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leucocytes.

  Naoki Yoshimura, Tokuma Tadami, Takaaki Kawaguchi, Minako Sako, Hiroshi Yoshimoto, Toshihiko Yamaka, Masakazu Takazoe
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  ABSTRACT: Hitherto, therapeutic depletion of granulocytes and monocytes by adsorption (GMA) has been associated with significant and insignificant efficacy in patients with ulcerative colitis (UC). Further, the processed blood volume in one GMA session has been fixed at 30 mL/min × 60 min, regardless of patients' body weight (BW). We were interested to see the efficacy and safety of GMA when administered in relation to patients' BW. Sixty patients were randomly assigned to the routine GMA (n = 30) and to GMA adjusted to patients' BW, 60 mL/kg (n = 30). GMA was done with the Adacolumn, up to 10 sessions over 10 weeks. At entry and 1 week post last GMA, patients were clinically and endoscopically evaluated. Remission was defined as clinical activity index (CAI) ≤4, whereas mucosal remission was defined as endoscopic index (EI) ≤3. In the BW group, the processed volume/session was 3,260 ± 581 versus 1,800 mL in the routine group (P < 0.001). In the BW group, 25 of 30 patients (83.3%) achieved remission versus 19 of 30 patients (63.3%) in the routine group. The average CAI in the BW group fell from 9.6 ± 2.6 to 2.3 ± 2.1 versus from 9.1 ± 2.4 to 4.0 ± 2.1 (P < 0.05) in the routine group. Similarly, the EI in the BW group fell from 9.4 ± 1.3 to 2.1 ± 2.1 versus from 9.2 ± 1.8 to 4.5 ± 2.3 (P < 0.01). GMA adjusted to patients' BW and at a vastly greater processed volume produces significantly higher efficacy as compared with the routine GMA protocol. Further, in this study, up to twofold higher processed volume caused no safety concern.
  Journal of Gastroenterology 09/2011; 47(1):49-55. · 4.16 Impact Factor
• Article: Conception and pregnancy outcome in women with inflammatory bowel disease: A multicentre study from Japan.

  Makoto Naganuma, Reiko Kunisaki, Naoki Yoshimura, Masakazu Nagahori, Hisae Yamamoto, Hideaki Kimura, Minako Sako, Takaaki Kawaguchi, Masakazu Takazoe, Shojiro Yamamoto, Toshiyuki Matsui, Toshifumi Hibi, Mamoru Watanabe
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  ABSTRACT: Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients. We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (<2500g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed. A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1-25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5-15.0) were significantly higher in Crohn's disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2-7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7-10.1) and LBW (OR 3.5, 95% CI: 1.3-9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery. In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection.
  Journal of Crohn s and Colitis 09/2011; 5(4):317-23. · 2.57 Impact Factor
• Article: HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn's disease.

  Yukinori Okada, Keiko Yamazaki, Junji Umeno, Atsushi Takahashi, Natsuhiko Kumasaka, Kyota Ashikawa, Tomomi Aoi, Masakazu Takazoe, Toshiyuki Matsui, Atsushi Hirano, Takayuki Matsumoto, Naoyuki Kamatani, Yusuke Nakamura, Kazuhiko Yamamoto, Michiaki Kubo
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  ABSTRACT: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 10⁻⁷⁰; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw*1202-B*5201-DRB1*1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10⁻³³; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10⁻²¹; OR = 2.65), but reduces risk for CD (P = 1.1 × 10⁻⁷; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10⁻¹⁹ and P = 7.2 × 10⁻⁵, respectively). The HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.
  Gastroenterology 06/2011; 141(3):864-871.e1-5. · 11.68 Impact Factor
• Article: Successful treatment of ulcerative colitis associated with hypereosinophilic syndrome/chronic eosinophilic leukemia.

  Nobuyasu Awano, Tomiko Ryu, Naoki Yoshimura, Masakazu Takazoe, Shigehiro Kitamura, Masanori Tanaka
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  ABSTRACT: A 23-year-old female was diagnosed as having simultaneous ulcerative colitis (UC) relapse and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL) without FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene. Pathological findings of colon specimens were compatible with UC, however, focal severe infiltration of eosinophils was observed in the rectum, which is unusual in UC, suggesting eosinophil-mediated organ damage. Although imatinib mesylate (IM) is usually ineffective for the treatment of HES/CEL with negative-F/P fusion gene, in the present case it led to the remission of HES/CEL and UC at a higher drug dosage level (400 mg/day). That suggested the presence of unknown tyrosine kinase abnormalities not yet categorized.
  Internal Medicine 01/2011; 50(16):1741-5. · 0.94 Impact Factor
• Article: The Efficacy of Asacol, a pH-Dependent Release Mesalamine Formulation in Patients With Ulcerative Colitis Who Showed Inadequate Response to the Time-Dependent Release Mesalamine Formulation, Pentasa

  Naoki Yoshimura, Tokuma Tadami, Takaaki Kawaguchi, Minako Sako, Abbi Saniabadi, Masakazu Takazoe
  Gastroenterology 01/2011; 140(5). · 11.68 Impact Factor
• Article: Free-breathing diffusion-weighted imaging for the assessment of inflammatory activity in Crohn's disease.

  Shigeru Kiryu, Keiichi Dodanuki, Hidemasa Takao, Makoto Watanabe, Yusuke Inoue, Masakazu Takazoe, Rikisaburo Sahara, Kiyohito Unuma, Kuni Ohtomo
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  ABSTRACT: To investigate the application of free-breathing diffusion-weighted MR imaging (DWI) to the assessment of disease activity in Crohn's disease. Thirty-one patients with Crohn's disease were investigated using free-breathing DWI without special patient preparation or IV or intraluminal contrast agent. The bowel was divided into seven segments, and disease activity was assessed visually on DWI. For quantitative analysis, the apparent diffusion coefficient (ADC) was measured in each segment. The findings of a conventional barium study or surgery were regarded as the gold standard for evaluating the diagnostic ability of DWI to assess disease activity. Upon visual assessment, the sensitivity, specificity, and accuracy for the detection of disease-active segments were 86.0, 81.4, and 82.4%, respectively. In the quantitative assessment, the ADC value in the disease-active area was lower than that in disease-inactive area in small and large bowels (1.61 +/- 0.44 x 10(-3) mm(2)/s versus 2.56 +/- 0.51 x 10(-3) mm(2)/s in small bowel and 1.52 +/- 0.43 x 10(-3) mm(2)/s versus 2.31 +/- 0.59 x 10(-3) mm(2)/s in large bowel, respectively, P<0.001). Free-breathing DWI is useful in the assessment of Crohn's disease. The accuracy of DWI is high in evaluating disease activity, especially in the small bowel, and the ADC may facilitate quantitative analysis of disease activity.
  Journal of Magnetic Resonance Imaging 05/2009; 29(4):880-6. · 2.70 Impact Factor
• Article: [A case of HIV infection associated with ulcerative colitis].

  Takaaki Kawaguchi, Minako Sako, Naoki Yoshimura, Masakazu Takazoe, Tomiko Ryu
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  ABSTRACT: We describe a 42-year-old-man with HIV infection who developed ulcerative colitis. Ulcerative colitis was diagnosed on the basis of clinical symptoms, and the findings of colonoscopy, pathology and culture. Although remission of ulcerative colitis was induced by PSL and SASP, HIV infection progressed. Treatment with highly active antiretroviral therapy (HAART) was started. HIV viral load decreased to less than 50copies/ml and CD4 counts increased to over 400/microl. After discontinuance of PSL and SASP, he is still in good condition. This is the first report of HIV infection associated with ulcerative colitis in Japan. A relationship between immune disorder in advanced HIV infection and inflammatory bowel disease was suggested. Ulcerative colitis might be an important complication in HIV infection.
  Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 05/2009; 106(4):536-41.
• Article: Sargramostim in patients with Crohn's disease: results of a phase 1-2 study.

  Masakazu Takazoe, Toshiyuki Matsui, Satoshi Motoya, Takayuki Matsumoto, Toshifumi Hibi, Mamoru Watanabe
  [show abstract] [hide abstract]
  ABSTRACT: We aimed to assess the tolerability, pharmacokinetics, safety, and efficacy of sargramostim in Japanese patients with active Crohn's disease (CD). Patients with moderately to severely active CD were enrolled. Step 1 was an open-label, phase 1 study of 2 microg/kg per day sargramostim administered subcutaneously (SC) for 4 weeks, with an optional 8-week extension with 6 microg/kg per day. Step 2 was an open-label, phase 1-2 study of the tolerability and pharmacokinetics of SC sargramostim 6 microg/kg per day over 4 weeks and of 8-week efficacy and safety. Efficacy variables were the proportion of patients achieving a clinical response [> or =100-point decrease from baseline in the CD activity index (CDAI)] and the proportion achieving clinical remission (CDAI < or = 150 points). Six patients participated in Step 1; five in Step 2. Serum concentrations of sargramostim peaked within 1 h of administration; mean terminal half-life was 2 h. Maximal serum concentrations increased with the dose. Mean accumulation ratios were 0.998 in Step 1 and 0.673 in Step 2. One of the six patients in the Step-1 extension and none of the five in Step 2 achieved a clinical response. Clinical remission was reported in one patient in each step. A notable decrease in median CDAI scores was observed in the extension and Step 2. In responders, improvement tended to be maintained through the 30-day follow-up. Drug-related adverse events included injection-site reaction, pyrexia, back pain, and bone pain. The systemic exposure of sargramostim increased dose-dependently. No accumulation in systemic exposure was associated with the repeated once-daily administration. SC sargramostim at 6 microg/kg per day improved median CDAI scores. A minority of patients experienced clinical remission or clinical response.
  Journal of Gastroenterology 04/2009; 44(6):535-43. · 4.16 Impact Factor
• Article: Hepatocellular carcinoma and Crohn's disease: a case report and review.

  Hideaki Miura, Takaaki Kawaguchi, Masakazu Takazoe, Shigehiro Kitamura, Haruki Yamada
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  ABSTRACT: Hepatocellular carcinoma (HCC) is usually known to develop in patients with underlying high-risk liver diseases such as viral hepatitis, cirrhosis and alcohol abuse, whereas reports dealing with HCC in Crohn's disease (CD) are limited. We present a case of HCC, which developed sequentially within a short period in a 52-year-old Japanese man with a 36-year history of CD without risky conditions for HCC. He also had not taken immunosuppressants such as azathioprine. Although the definitive etiological factors contributing to hepatocarcinogenesis in the present case could not be elucidated, further close surveillance is required.
  Internal Medicine 02/2009; 48(10):815-9. · 0.94 Impact Factor
• Article: Positive association of genetic variants in the upstream region of NKX2-3 with Crohn's disease in Japanese patients.

  K Yamazaki, A Takahashi, M Takazoe, M Kubo, Y Onouchi, A Fujino, N Kamatani, Y Nakamura, A Hata
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  ABSTRACT: A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17,000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM, NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay. A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype-phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.
  Gut 11/2008; 58(2):228-32. · 10.11 Impact Factor
• Article: Drug-induced hypersensitivity syndrome associated with reactivation of human herpesvirus 6 presenting with severe hepatic injury

  Hideaki Miura, Masayuki Nakano, Naoki Yoshimura, Shigehiro Kitamura, Haruki Yamada, Masakazu Takazoe
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  ABSTRACT: Little is known about the pathophysiology of liver complication seen in drug-induced hypersensitivity syndrome (DIHS). We describe herein a 32-year-old Japanese man with DIHS due to salazosulfapyridine (SASP) associated with reactivation of human herpesvirus6 (HHV-6) presenting with severe acute hepatic injury. The patient, with a 1-year history of ulcerative colitis (UC), presented with high fever and abnormally elevated liver enzymes. Six weeks prior to his symptoms, prednisolone (PSL) and SASP had been started because of UC aggravation. Besides fever and liver dysfunction, the appearance of atypical lymphocytes together with eosinophils and generalized erythematous maculopapular skin rash developed sequentially, and a diagnosis of DIHS was established. Despite cessation of SASP and increased dose of PSL, his initial abnormalities continued, and biphasic second alanine aminotransferase (ALT) flare with deep jaundice worsened. Based on the significant increase in the titer of HHV-6 IgG antibodies at the second peak of ALT level without HHV-6 IgM antibody elevation, strongly suggesting reactivation of the virus, HHV-6 was first considered to directly contribute to the deterioration of liver function. However, extensive histological analysis of the liver led to the realization that the cause of the DIHS liver injury was essentially drug-related hepatotoxicity induced by SASP, causing wide-ranging damage to both the hepatocytes and cholangiocytes.
  Clinical Journal of Gastroenterology 09/2008; 1(3):127-132.
• Article: Oral spherical adsorptive carbon for the treatment of intractable anal fistulas in Crohn's disease: a multicenter, randomized, double-blind, placebo-controlled trial.

  Yoshihiro Fukuda, Masakazu Takazoe, Akira Sugita, Tadashi Kosaka, Fukunori Kinjo, Yoshimasa Otani, Hisao Fujii, Kazutaka Koganei, Kazuya Makiyama, Toshio Nakamura, [......], Shojiro Yamamoto, Toshifumi Ashida, Akira Majima, Norikazu Morita, Kazunari Murakami, Nobuhide Oshitani, Kazuya Takahama, Masahiro Tochihara, Tomoyuki Tsujikawa, Makoto Watanabe
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  ABSTRACT: Anal fistulas are common in individuals with Crohn's disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD. In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also assessed. In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed. AST-120 is useful for the control of intractable anal fistulas in CD patients.
  The American Journal of Gastroenterology 07/2008; 103(7):1721-9. · 7.28 Impact Factor