Efficacy and Safety of Long-Term Thiopurine Maintenance Treatment in Japanese Patients With Ulcerative Colitis

BACKGROUND/AIMS: The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. METHODS: This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remission-maintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurine as maintenance treatment. RESULTS: The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5-aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events. CONCLUSIONS: Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC.

Efficacy of Thiopurines in Biologic-Naive Japanese Patients With Crohn's Disease: A Single-Center Experience

BACKGROUND/AIMS: Early use of biologics in patients with Crohn's disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulators in patients with CD. METHODS: Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance. RESULTS: The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non-relapse and relapse groups (P=0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history of surgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months; P=0.036). CONCLUSIONS: Thiopurine use might be beneficial for the long-term maintenance of remission in biologic-naive Crohn's disease patients without digestive complications and a history of surgery.

Usefulness of Adalimumab for Treating a Case of Intestinal Behcet's Disease With Trisomy 8 Myelodysplastic Syndrome

Behcet's disease (BD) is a systemic vasculitis, while myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized by ineffective hematopoiesis. Some studies suggest a relationship between MDS and BD, especially intestinal BD, and trisomy 8 seems to play an important role in both diseases. There are several reports on patients with BD comorbid with MDS involving trisomy 8 that frequently have intestinal lesions refractory to conventional medical therapies. Tumor necrosis factor (TNF)-alpha is strongly involved in the pathophysiology of several autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and BD. In addition, TNF-alpha plays an important role in the pathophysiology of MDS by inhibiting normal hematopoiesis and inducing the programmed cell death of normal total bone marrow cells and normal CD34+ cells. Recent clinical reports demonstrate the favorable effect of TNF-alpha antagonists in patients with refractory intestinal BD and in those with MDS. We present the case of a patient with intestinal BD and MDS involving trisomy 8 who was successfully treated with adalimumab.

Experimental Studies of Concentration of Organophosphorous Pesticides in the Living Body / 日本農村医学会雑誌

In the previous report, we concluded that chances are very slim for Salithion and Sumithion to concentrate in rabbits as these organophosphorous compounds are excreted quickly. This conclusion was inferentially drawn from the results of measurements of concentration of Salithion and Sumithion residues in the blood after experimental exposures of rabbits to the pesticides.<BR>In the present report, we will discuss the same toxicological problem based on our findings in a series of experiments using rabbits with hepatic disturbances induced by carbon tetrachloride (CCl<SUB>4</SUB>).<BR>Rabbits were divided into three groups. One consists of rabbits having light hepatic disorder. They were subcutaneously injected with 0.1ml/kg of 20% CCl4 olive oil for three days consecutively. Under the second group come rabbits with moderate liver disturbance caused by the injection of 0.3 ml/kg of 20% CCl<SUB>4</SUB> olive oil. The injection was also made for three days. The remaining group is the control group.<BR>These rabbits were administered orally with 5mg/kg and 20mg/kg of Smithion for three days running.<BR>The examination covered (1) Sumithion residue level in the blood, (2) PNMC level in urine, (3) hepatic function (ChE, GOT, GPT, BSP, Al-P, BUN), (4) urinalysis and (5) histopathological examination of the liver and the kidney. The results of these tests were studied in comparison with those of the control group.<BR>The following is a summary of our conclusion:<BR>1) In the control group, Sumithion residues in the blood disappeared quickly, and could not be detected 72 hours after administration.<BR>2) As far as the disappearance of Sumithion and the excretion of PNMC are concerned, there was no significant difference between the control and the light and moderate liver disturbance groups of rabbits.<BR>3) In the rabbits with CCl<SUB>4</SUB>-induced liver disturbances, it was noted that the administration of Sumithion impeded serum and red-cell ChE activities to a remarkable extent, and delayed the recovery of the liver function.<BR>4) However, the liver disturbance did not deteriorate. The histological observation of the liver and the kidney did not reveal any abnormality due to the administration of Sumithion, either.

Experimental Studies on Residue of the Administered Organophosphorous Insecticides / 日本農村医学会雑誌

Each of the 1, 000-times dilute solution of both drugs, Salithion and Sumithion, were experimentally sprayed over rabbits in vinyl greenhouses at a rate of five hours a day for three consecutive days. Changes in the residual quantity of the drugs in the blood and also in the quantity of PNMC, a metabolite of Sumithion in urine, were measured with the passage of time after the spraying. At the same time, the liver functions of the rabbits were checked and they were also subjected to a urinalysis and a pathohistological examination. The conclusions drawn from these studies are as follows:<BR>1) No abnormal findings were observed on the appearance of the rabbits exposed to Salithion and Sumithion. Nor were there any abnormalities in the ophthalmologic findings, especially, in the funduscopic findings, at 10 and 30 days after the spraying of these drugs.<BR>2) The residual quantity of both drugs in all the experimented rabbit's blood was measured immediately after the spraying. However, these drugs later disappeared rapidly from the blood, and they could not be detected 10 days after the spraying.<BR>3) There was a significant rise in the quantity of PNMC 24 hours after the spraying. Later, it decreased rapidly. Ten days after the spraying, its values returned to normal level before the spraying.<BR>4) With respect to the serum ChE level, the changes in the groups exposed to Salithion and Sumithion were the same as those in the control groups. So, any influences were not observed on serum ChE by the spraying of these drugs.<BR>5) In the liver function test, urinalysis and pathohistological examination, no abnomal findings attributable to the inhalation of both drugs were observed.<BR>6) The drug concentration in the air in the vinyl greenhouses at the time of their spraying was 61.5μg/m<SUP>3</SUP> for Salithion and 30.1μg/m<SUP>3</SUP> for Sumithion.