Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease.

Abstract:

OBJECTIVES:There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease. The purpose of this study was to assess the relation between clinical response, 6-mercaptopurine metabolite levels, relative leukopenia, and drug dose. METHODS:60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for > or = 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated. Patients were classified as complete responders (N = 24), partial responders (N = 7), or non-responders (N = 29). RESULTS:Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight (P = 0.002). 6-Thioguanine levels also were associated with clinical response (P = 0.003) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 x 10(8) RBC. Relative leukopenia, defined as white blood cell count less than either 5.0 or 4.0 K/uL, was not associated with clinical response (P = 0.13 and 0.77 respectively). CONCLUSIONS:1. Drug dose and 6-thioguanine levels are related to clinical response in patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine. 2. For 6-thioguanine levels, there is a fair amount of overlap, but maximal differentiation between responders and non-responders is seen at levels > 260 pmol/8 x 10(8) RBC. 3. Relative leukopenia does not correlate well with clinical response.

journal_name

Inflamm Bowel Dis

authors

Achkar JP,Stevens T,Easley K,Brzezinski A,Seidner D,Lashner B

doi

10.1097/00054725-200407000-00003

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

339-45

issue

4

eissn

1078-0998

issn

1536-4844

pii

00054725-200407000-00003

journal_volume

10

pub_type

临床试验,杂志文章
  • Tissue-nonspecific alkaline phosphatase is activated in enterocytes by oxidative stress via changes in glycosylation.

    abstract:BACKGROUND:Intestinal inflammation produces an induction of alkaline phosphatase (AP) activity that is attributable in part to augmented expression, accompanied by a change in isoform, in epithelial cells. METHODS:This study focuses on induction of AP in intestinal epithelial cells in vitro. RESULTS:Treatment with th...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21381

    authors: López-Posadas R,González R,Ballester I,Martínez-Moya P,Romero-Calvo I,Suárez MD,Zarzuelo A,Martínez-Augustin O,Sánchez de Medina F

    更新日期:2011-02-01 00:00:00

  • Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis.

    abstract:BACKGROUND:Activation of cannabinoid (CB)(1) receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB(2) receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB(2) recept...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20960

    authors: Storr MA,Keenan CM,Zhang H,Patel KD,Makriyannis A,Sharkey KA

    更新日期:2009-11-01 00:00:00

  • The IBD-F Patient Self-Assessment Scale Accurately Depicts the Level of Fatigue and Predicts a Negative Effect on the Quality of Life of Patients With IBD in Clinical Remission.

    abstract:BACKGROUND:Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD) and may have an unfavorable impact on quality of life (QoL). The IBD-Fatigue scale (with components SCORE1 and SCORE2) is a recently developed disease-specific questionnaire. We sought to validate a Greek version of IBD-F and us...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa201

    authors: Varbobitis I,Kokkotis G,Gizis M,Perlepe N,Laoudi E,Bletsa M,Bekiari D,Koutsounas I,Kounadis G,Xourafas V,Lagou S,Kolios G,Papakonstantinou I,Bamias G

    更新日期:2020-08-07 00:00:00

  • Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.

    abstract:BACKGROUND:Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an obje...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000376

    authors: Huang VW,Prosser C,Kroeker KI,Wang H,Shalapay C,Dhami N,Fedorak DK,Halloran B,Dieleman LA,Goodman KJ,Fedorak RN

    更新日期:2015-06-01 00:00:00

  • The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic acid-induced colitis in rats: an experimental study.

    abstract::The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrob...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/00054725-200403000-00008

    authors: Kara E,Sungurtekin H,Sungurtekin U,Alkanat M,Ilkgul O

    更新日期:2004-03-01 00:00:00

  • Different Profile of Efficacy of Thiopurines in Ulcerative Colitis and Crohn's Disease.

    abstract:BACKGROUND:Thiopurines are effective drugs in treating ulcerative colitis (UC) and Crohn's disease (CD) even if studies that specifically investigate these drugs' profile of efficacy in UC compared with CD are scarce. Our aim was to compare the profile of efficacy of thiopurines in patients with UC and CD. METHODS:We ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000538

    authors: Rispo A,Testa A,De Palma GD,Donetto S,Diaferia M,Musto D,Nardone O,Maione F,Caporaso N,Castiglione F

    更新日期:2015-11-01 00:00:00

  • Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD)-associated dysbiosis is characterized by a loss of Faecalibacterium prausnitzii, whose supernatant exerts an anti-inflammatory effect. However, the anti-inflammatory substances in F. prausnitzii supernatant and the mechanism in ameliorating colitis in IBD have not yet been fu...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy182

    authors: Zhou L,Zhang M,Wang Y,Dorfman RG,Liu H,Yu T,Chen X,Tang D,Xu L,Yin Y,Pan Y,Zhou Q,Zhou Y,Yu C

    更新日期:2018-08-16 00:00:00

  • Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease.

    abstract:BACKGROUND:Noninvasive, sensitive, and specific tools for early identification of chronic inflammatory bowel disease (IBD) are needed for clinical practice. The aim was to identify new noninvasive test combinations for characterization of IBD in children and adolescents by comparing serological responses to microbial a...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20535

    authors: Ashorn S,Honkanen T,Kolho KL,Ashorn M,Välineva T,Wei B,Braun J,Rantala I,Luukkaala T,Iltanen S

    更新日期:2009-02-01 00:00:00

  • Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study).

    abstract:BACKGROUND:The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS:Patients diagnosed with inflammator...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.MIB.0000225339.91484.fc

    authors: Henriksen M,Jahnsen J,Lygren I,Sauar J,Kjellevold Ø,Schulz T,Vatn MH,Moum B,IBSEN Study Group.

    更新日期:2006-07-01 00:00:00

  • Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell-Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been un...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz191

    authors: Jamwal DR,Marati RV,Harrison CA,Midura-Kiela MT,Figliuolo Paz VR,Besselsen DG,Ghishan FK,Kiela PR

    更新日期:2020-01-06 00:00:00

  • Safety and tolerability of human placenta-derived cells (PDA001) in treatment-resistant crohn's disease: a phase 1 study.

    abstract:BACKGROUND:The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn's disease. METHODS:Twelve subjects with active, moderate-...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1097/MIB.0b013e31827f27df

    authors: Mayer L,Pandak WM,Melmed GY,Hanauer SB,Johnson K,Payne D,Faleck H,Hariri RJ,Fischkoff SA

    更新日期:2013-03-01 00:00:00

  • L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.

    abstract:BACKGROUND:L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to det...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000790

    authors: Coburn LA,Horst SN,Allaman MM,Brown CT,Williams CS,Hodges ME,Druce JP,Beaulieu DB,Schwartz DA,Wilson KT

    更新日期:2016-08-01 00:00:00

  • In vivo imaging of reactive oxygen and nitrogen species in murine colitis.

    abstract:BACKGROUND:Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent pr...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000118

    authors: Asghar MN,Emani R,Alam C,Helenius TO,Grönroos TJ,Sareila O,Din MU,Holmdahl R,Hänninen A,Toivola DM

    更新日期:2014-08-01 00:00:00

  • Low-dose oral ferrous fumarate aggravated intestinal inflammation in rats with DSS-induced colitis.

    abstract:BACKGROUND:Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in ra...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.mib.0000174374.83601.86

    authors: Erichsen K,Milde AM,Arslan G,Helgeland L,Gudbrandsen OA,Ulvik RJ,Berge RK,Hausken T,Berstad A

    更新日期:2005-08-01 00:00:00

  • Natural History of  Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

    abstract:BACKGROUND:The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. METHODS:We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North Amer...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa080

    authors: Kerur B,Benchimol EI,Fiedler K,Stahl M,Hyams J,Stephens M,Lu Y,Pfefferkorn M,Alkhouri R,Strople J,Kelsen J,Siebold L,Goyal A,Rosh JR,LeLeiko N,Van Limbergen J,Guerrerio AL,Maltz R,Karam L,Crowley E,Griffiths A,H

    更新日期:2020-05-09 00:00:00

  • Short CDAI: development and validation of a shortened and simplified Crohn's disease activity index.

    abstract:BACKGROUND:The aim of this study was to develop a shortened Crohn's Disease Activity Index (CDAI). METHODS:A short CDAI was developed retrospectively using patient-level data from four budesonide clinical trials to select variables from the full CDAI which best predicted health-related quality of life as measured by t...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21400

    authors: Thia K,Faubion WA Jr,Loftus EV Jr,Persson T,Persson A,Sandborn WJ

    更新日期:2011-01-01 00:00:00

  • Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with inactive ulcerative colitis.

    abstract:BACKGROUND:We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been establi...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20042

    authors: Casellas F,Borruel N,Antolín M,Varela E,Torrejón A,Armadans L,Guarner F,Malagelada JR

    更新日期:2007-04-01 00:00:00

  • The Management of Intestinal Penetrating Crohn's Disease.

    abstract::Crohn's disease (CD) leads to the development of complications through progressive uncontrolled inflammation and the transmural involvement of the bowel wall. Most of the available literature on penetrating CD focuses on the perianal phenotype. The management of nonperianal penetrating complications poses its own set ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1093/ibd/izx108

    authors: Hirten RP,Shah S,Sachar DB,Colombel JF

    更新日期:2018-03-19 00:00:00

  • Oral mesalazine (5-ASA) treatment may protect against proximal extension of mucosal inflammation in ulcerative proctitis.

    abstract:OBJECTIVES:Studies aimed at establishing which characteristics of patients with ulcerative proctitis could be predictive of the extension of inflammation have failed to provide conclusive results. The aim of the study was to evaluate the prognostic role of clinical and therapeutic parameters in patients with proctitis....

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/00054725-200411000-00006

    authors: Pica R,Paoluzi OA,Iacopini F,Marcheggiano A,Crispino P,Rivera M,Bella A,Consolazio A,Paoluzi P

    更新日期:2004-11-01 00:00:00

  • PKR protects colonic epithelium against colitis through the unfolded protein response and prosurvival signaling.

    abstract:BACKGROUND:The dsRNA-activated protein kinase (PKR) phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a global regulator of protein synthesis in mammals. In addition, PKR activates several signal transduction pathways including STAT3 and AKT. PKR is activated by a number of inflammator...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.22878

    authors: Cao SS,Song B,Kaufman RJ

    更新日期:2012-09-01 00:00:00

  • Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis.

    abstract:INTRODUCTION:Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000001025

    authors: Targownik LE,Tennakoon A,Leung S,Lix LM,Nugent Z,Singh H,Bernstein CN

    更新日期:2017-03-01 00:00:00

  • miR-29a-5p/STAT3 Positive Feedback Loop Regulates TETs in Colitis-Associated Colorectal Cancer.

    abstract:BACKGROUND:Interleukin (IL)-6/signal transducers and activators of transcription 3 (STAT3) signaling plays an important role in the development of colitis-associated colorectal cancer (CAC). The mechanism of CAC formation remains unclear, and the relationship between miRNAs and the IL-6/STAT3 signaling pathway in the d...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz281

    authors: Wang A,Deng S,Chen X,Yu C,Du Q,Wu Y,Chen G,Hu L,Hu C,Li Y

    更新日期:2020-03-04 00:00:00

  • Assessing Small Bowel Stricturing and Morphology in Crohn's Disease Using Semi-automated Image Analysis.

    abstract:BACKGROUND:Evaluating structural damage using imaging is essential for the evaluation of small intestinal Crohn's disease (CD), but it is limited by potential interobserver variation. We compared the agreement of enterography-based bowel damage measurements collected by experienced radiologists and a semi-automated ima...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz196

    authors: Stidham RW,Enchakalody B,Waljee AK,Higgins PDR,Wang SC,Su GL,Wasnik AP,Al-Hawary M

    更新日期:2020-04-11 00:00:00

  • Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists knowledge.

    abstract:BACKGROUND:Current therapy for inflammatory bowel disease (IBD) patients often involves agents that suppress the immune system, placing patients at an increased risk for developing infections, of which several are potentially vaccine preventable. Many IBD patients are not being vaccinated appropriately. The aims of thi...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/ibd.21667

    authors: Wasan SK,Coukos JA,Farraye FA

    更新日期:2011-12-01 00:00:00

  • Therapy with anti-TNFα antibody enhances number and function of Foxp3(+) regulatory T cells in inflammatory bowel diseases.

    abstract:BACKGROUND:Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4(+) CD25(+) Foxp3(+) T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of I...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21308

    authors: Boschetti G,Nancey S,Sardi F,Roblin X,Flourié B,Kaiserlian D

    更新日期:2011-01-01 00:00:00

  • Genotype-phenotype analysis in childhood-onset Crohn's disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease.

    abstract:INTRODUCTION:The incidence of early-onset CD in Scotland is among the highest worldwide. Three single nucleotide polymorphisms (SNPs) R702W, G908R and Leu1007finsC in the NOD2/CARD15 gene predispose to adult CD. We investigated the contribution of these variants to disease susceptibility and phenotype in the Scottish e...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.mib.0000183423.38037.f3

    authors: Russell RK,Drummond HE,Nimmo EE,Anderson N,Smith L,Wilson DC,Gillett PM,McGrogan P,Hassan K,Weaver LT,Bisset M,Mahdi G,Satsangi J

    更新日期:2005-11-01 00:00:00

  • MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease.

    abstract:BACKGROUND:To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS:A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20044

    authors: Mendoza JL,Urcelay E,Lana R,Martín MC,López N,Guijarro LG,Mayol JA,Taxonera C,de la Concha EG,Peña AS,Díaz-Rubio M

    更新日期:2007-05-01 00:00:00

  • Diagnostic Performance of a 5-Marker Predictive Model for Differential Diagnosis Between Intestinal Tuberculosis and Crohn's Disease.

    abstract:Background:The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods:A total of 268 patients who were suspected of having ITB or CD were prospectively recruited be...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy154

    authors: Wu X,Huang H,Hou H,Shen G,Yu J,Zhou Y,Bosco MJ,Mao L,Wang F,Sun Z

    更新日期:2018-10-12 00:00:00

  • Two-stage genome-wide methylation profiling in childhood-onset Crohn's Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci.

    abstract:BACKGROUND:As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onse...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000179

    authors: Adams AT,Kennedy NA,Hansen R,Ventham NT,OʼLeary KR,Drummond HE,Noble CL,El-Omar E,Russell RK,Wilson DC,Nimmo ER,Hold GL,Satsangi J

    更新日期:2014-10-01 00:00:00

  • A new oral delivery system for 5-ASA: preliminary clinical findings for MMx.

    abstract:BACKGROUND:Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how ...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/01.mib.0000158386.25660.1e

    authors: Prantera C,Viscido A,Biancone L,Francavilla A,Giglio L,Campieri M

    更新日期:2005-05-01 00:00:00