A Randomized, Double-Blind, Controlled Withdrawal Trial in Crohn’s Disease Patients in Long-term Remission on Azathioprine

Lémann, Marc; Mary, Jean‐Yves; Colombel, Jean–Frédéric; Duclos, Bernard; Soulé, Jean–Claude; Lerebours, Éric; Modigliani, R; Bouhnik, Yoram

doi:10.1053/j.gastro.2005.03.031

Cited by 331 publications

(210 citation statements)

References 33 publications

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“…10 The study by Lemann et al was designed as a noninferiority study, and the investigators concluded that they could not reject the hypothesis that placebo was inferior to continuing azathioprine. 8 The other 3 RCTs showed higher relapse rates in the drug withdrawal arm compared with the drug continuation arm (P < .05), but statistical significance was lost in one study at longer follow-up. 10 Of the RCTs, Treton et al 20 reported the highest relapse rates at 12 months but was the only one that was not placebo controlled.…”

Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 93%

“…These comprised 5 RCTs 8-12 and 13 retrospective cohort studies [13][14][15][16][17][18][19][20][21][22][23][24][25] (one of which 20 was an extension study from a previous RCT 8 ). Eleven studies reported on immunomodulator withdrawal in CD [8][9][10][11]14,15,17,20,[23][24][25] and 8 in UC. 12,13,[17][18][19]21,22,24 One study by Fraser et al reported on long-term outcomes of patients treated with methotrexate and presented relapse rates for IBD with no distinction between CD and UC.…”

Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 99%

“…All 4 RCTs in CD reported higher relapse rates after stopping the immunomodulator compared with continuing the drug. [8][9][10][11] All RCTs focused on azathioprine exclusively and the longest follow-up was for 2 years after withdrawal. 10 The study by Lemann et al was designed as a noninferiority study, and the investigators concluded that they could not reject the hypothesis that placebo was inferior to continuing azathioprine.…”

Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 99%

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Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

et al. 2015

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Little is known about the optimal duration of therapy with an anti-tumor necrosis factor (TNF) agent and/or an immunomodulator for patients with inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (drug cessation or dose reduction) of anti-TNF agents and/or immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de-escalation [drug cessation or dose reduction] of immunomodulator monotherapy, 8 on immunomodulator de-escalation from combination therapy, and 43 on de-escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with Crohn's disease or ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after therapy was stopped). Most studies of patients with Crohn's disease who discontinued an immunomodulator after combination therapy found that rates of relapse did not differ from those of patients who continued taking the drug (55%-60% had disease relapse 24 months after they stopped taking the immunomodulator). The only study in patients with ulcerative colitis supported continued immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost.Keywords : Crohn's Disease ; Ulcerative Colitis ; Patient Management ; Cessation.Abbreviations used in this paper : anti-TNF, anti-tumor necrosis factor therapy ; CD, Crohn's disease ; CRP, C-reactive protein ; FC, fecal calprotectin ; IBD, inflammatory bowel disease ; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses ; RCT, randomized controlled trial ; TNF, tumor necrosis factor ; UC, ulcerative colitis.Therapeutic strategies in inflammatory bowel disease (IBD) have evolved considerably in the past few decades. The acknowledgment that subclinical and undertreated inflammation can lead to poor outcomes has underpinned a shift in treatment goals from symptomatic control to sustained clinical and endoscopic remission.1 Treatment strategies have changed accordingly, including the ear...

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Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 93%

Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 99%

Section: De-escalation Of Immunomodulator Monotherapymentioning

confidence: 99%

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Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

et al. 2015

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“…It remains to be determined how to " optimize " dose and whether induction of leukopenia or therapeutic monitoring of 6-thioguanine metabolites o ers improved means of assuring a long-term response. Nevertheless, clinical trials have demonstrated that azathioprine at doses of 2.0 -2.5 mg / kg and 6-mercaptopurine at a dose of 1.5 mg / kg have been e ective at maintaining remissions for, at least, 4 years (213) . Complete blood counts must be monitored carefully early in the course of treatment and in the long term, at a minimum of every 3 months, because of the risk of delayed bone marrow suppression remission (230,231) .…”

Section: Maintenance Therapymentioning

confidence: 99%

Management of Crohn's Disease in Adults

2009

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Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifi cally valid research, derived from extensive review of published literature. When data that will withstand objective scrutiny are not available, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be fl exible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are infl exible and rarely violated. Given the wide range of choices in any health-care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. Expert opinion is solicited from the outset for the document. The quality of evidence upon which a specifi c recommendation is based is as follows: Grade A: Homogeneous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of suffi cient statistical power. Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case -control analytic studies, or well-designed meta-analysis. Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fi elds. The fi nal recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientifi c developments at a later time.

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“…Porem a 6-MP, seguida por metotrexato, são também uma opção em casos de intolerância à azatioprina (LÉMANN et al, 2005) São medicamentos seguros que podem ser usadas durante a gravidez (CARTER; LOBO;TRAVIS, 2004). Porém podem surgir efeitos desfavoráveis de imunossupressão, que ocorrem em cerca de 20% dos casos, na maioria das vezes entre 2 a 3 semanas após o início da terapia, e compreendem principalmente reações alérgicas, leucopenia e hepatotoxicidade (PEARSON et al, 2000).…”

Section: Imunomodeladoresunclassified

Doença De Crohn

Papacosta¹,

Nunes²,

Pacheco³

et al. 2017

Rev Pat Tocantins

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INTRODUÇÃO: A doença de Crohn é qualificada como uma doença inflamatória intestinal, de caráter crônico, recidivante, transmural e que pode afetar qualquer parte do trato digestivo, desde a boca até o ânus, mas, principalmente, o intestino delgado e o cólon. São de cunho multifatorial, com prevalência e incidência variando de acordo com a genética, meio ambiente, microbiota intestinal e até mesmo um possível agente entérico infeccioso. É uma doença que afeta pessoas de várias idades, sexos e raças, apesar de se verificar maior incidência em jovens do sexo feminino e em regiões urbanas. METODOLOGIA: Trata-se de um artigo de revisão no qual, a partir das palavras “doença de Crohn” e “doença inflamatórias intestinais”, foi realizado busca por periódicos nos bancos de dados: PubMed, Scielo, Portal Periódicos CAPES e Google acadêmico. CONCLUSÃO: A doença de Crohn apresenta uma importante taxa de morbimortalidade no mundo, principalmente em regiões em franca urbanização e industrialização. O diagnóstico é um procedimento extremamente complicado devido a sua clínica inespecífica e pelos vários aspetos em comum com outras patologias. Dessa forma, ainda se faz necessário uma melhor investigação científica na área, com intuito de se desenvolver melhores técnicas diagnosticas e condutas a serem tomadas no seguimento e cura dessa patologia.Palavras-chave: Doença de Crohn, Doença inflamatórias intestinais, Diarreia. ABSTRACT INTRODUCTION: Crohn's disease is described as an inflammatory, chronic, recurrent, transmural inflammatory disease that can affect any part of the digestive tract, from the mouth to the anus, but especially the small intestine and colon. They are multifactorial, with prevalence and incidence varying according to genetics, environment, intestinal microbiota and even a possible infectious enteric agent. It is a disease that affects people of various ages, sexes and races, although there is a greater incidence in young women and in urban areas. METHODOLOGY: This is a review article in which, from the words "Crohn's disease" and "inflammatory bowel disease", a search was made for journals in the databases: PubMed, Scielo, Portal Periódicos CAPES and Google academic. CONCLUSION: Crohn's disease presents an important morbidity and mortality rate in the world, especially in regions where there is rapid urbanization and industrialization. Diagnosis is an extremely complicated procedure due to its nonspecific clinical and various aspects in common with other pathologies. Thus, a better scientific investigation in the area is still necessary, in order to develop better diagnostic techniques and behaviors to be taken in the follow-up and cure of this pathology. Keywords: Crohn's disease, Inflammatory bowel disease, Diarrhea.

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A Randomized, Double-Blind, Controlled Withdrawal Trial in Crohn’s Disease Patients in Long-term Remission on Azathioprine

Cited by 331 publications

References 33 publications

Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

Management of Crohn's Disease in Adults

Doença De Crohn

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