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Acta Dermatovenerologica Croatica : ADC 2007Azathioprine is a synthetic purine analog derived from 6-mercaptopurine. It is a purine antagonist and its active metabolites act by disrupting the function of... (Review)
Review
Azathioprine is a synthetic purine analog derived from 6-mercaptopurine. It is a purine antagonist and its active metabolites act by disrupting the function of endogenous purines. It has a cytotoxic and immunosuppressive mechanism of action. It is used in dermatology for treatment of immunobullous diseases, generalized eczematous disorders and photodermatoses. There is an enzyme in the metabolism of azathioprine called thiopurine s-methyltransferase (TPMT). It is very important to measure the TPMT activity before initiating therapy so that proper dosing of azathioprine can be achieved.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Skin Diseases
PubMed: 18093457
DOI: No ID Found -
Journal of the American Academy of... Aug 1991Azathioprine has been available for 30 years and is used in a variety of dermatologic conditions. In common with other systemic immunosuppressant drugs, it has... (Review)
Review
Azathioprine has been available for 30 years and is used in a variety of dermatologic conditions. In common with other systemic immunosuppressant drugs, it has potentially serious side effects in both the short and the long term. It has a favorable therapeutic ratio, however, and most side effects can be avoided by administering low doses for short periods. This review describes azathioprine's chemistry, drug interactions, adverse effects, and oncogenicity and then deals with its clinical applications. The well-established uses are discussed first, followed by less conventional ones. In severe, potentially fatal blistering diseases, azathioprine has an undisputed place in management. For intractable, disabling actinic reticuloid and atopic eczema, it has a smaller part to play, and its role is less clear.
Topics: Azathioprine; Drug Interactions; Eczema; Humans; Leukopenia; Pemphigoid, Bullous; Pemphigus; Skin Diseases
PubMed: 1918467
DOI: 10.1016/0190-9622(91)70196-9 -
Clinics in Rheumatic Diseases Aug 1984
Topics: Arthritis; Arthritis, Rheumatoid; Azathioprine; Female; Gastrointestinal Diseases; Humans; Leukopenia; Lupus Erythematosus, Systemic; Male; Neoplasms; Psoriasis; Risk
PubMed: 6509884
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2009The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis was performed to evaluate the efficacy of these agents for the maintenance of remission of quiescent Crohn's disease.
OBJECTIVES
To assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of remission in quiescent Crohn's disease.
SEARCH STRATEGY
Pertinent studies were selected using the MEDLINE data base (1966-May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease register, as well as abstracts from major gastrointestinal research meetings and references from published articles and review. This search strategy was updated (1998-May 2008) using the MEDLINE, EMBASE and International Pharmaceutical Abstracts databases, the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register.
SELECTION CRITERIA
Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with quiescent Crohn's disease.
DATA COLLECTION AND ANALYSIS
Data were extracted by three independent observers (EP, MC, LRS) based on the intention to treat principle. Peto odds ratios and 95% confidence intervals for maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.
MAIN RESULTS
Seven trials of azathioprine therapy and one of 6-mercaptopurine were included in the review. Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission. The Peto odds ratio (OR) for maintenance of remission with azathioprine was 2.32 (95% CI 1.55 to 3.49) with a NNT of 6. The Peto OR for maintenance of remission with 6-mercaptopurine was 3.32 (95% CI 1.40 to 7.87) with a of 4. Higher doses of azathioprine improved response. A steroid sparing effect with azathioprine was noted, with a Peto OR of 5.22 (95% CI 1.06 to 25.68) and NNT of 3 for quiescent disease. Withdrawals due to adverse events were more common in patients treated with azathioprine (Peto OR 3.74; 95% CI 1.48 to 9.45, NNH = 20) than with placebo.
AUTHORS' CONCLUSIONS
Azathioprine and 6-mercaptopurine are more effective than placebo for maintenance of remission in Crohn's disease. Higher response rates were obtained with azathioprine than 6-mercaptopurine. However, the one study evaluating 6-mercaptopurine used a relatively low dose of the drug. Future studies should look at the effect of higher doses of 6-mercaptopurine. There is weak evidence for a steroid sparing effect with azathioprine treatment.
Topics: Azathioprine; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Prodrugs; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 19160175
DOI: 10.1002/14651858.CD000067.pub2 -
Clinical and Experimental Dermatology Feb 2022
Topics: Azathioprine; Dermatology; Genotype; Humans; Methyltransferases; Polymorphism, Genetic
PubMed: 34609021
DOI: 10.1111/ced.14915 -
Dermatologic Therapy 2007Azathioprine, a prodrug of 6-mercaptopurine, was developed over four decades ago. Since its development, azathioprine has been shown to have antileukemic,... (Review)
Review
Azathioprine, a prodrug of 6-mercaptopurine, was developed over four decades ago. Since its development, azathioprine has been shown to have antileukemic, anti-inflammatory, and immunosuppressive properties. Hence, the reason azathioprine is used in multiple medical specialties. In the dermatology field, it is used as an immunosuppressant and corticosteroid-sparing agent for the treatment of several cutaneous diseases. In this article, the present authors review the following aspects relating to azathioprine: history, pharmacokinetics, significance of thiopurine methyltransferase, side effects, contraindications, therapeutic uses, and recommended evaluation and monitoring for patients initiating azathioprine.
Topics: Animals; Azathioprine; Humans; Methyltransferases; Practice Guidelines as Topic; Skin Diseases
PubMed: 17970886
DOI: 10.1111/j.1529-8019.2007.00134.x -
The Cochrane Database of Systematic... 2000To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease. (Review)
Review
OBJECTIVES
To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease.
SEARCH STRATEGY
Pertinent studies were selected using the MEDLINE data base (1966 - May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews.
SELECTION CRITERIA
Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission.
DATA COLLECTION AND ANALYSIS
Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.
MAIN RESULTS
Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19.
REVIEWER'S CONCLUSIONS
Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.
Topics: Azathioprine; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Prodrugs
PubMed: 10796482
DOI: 10.1002/14651858.CD000067 -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Azathioprine; Carcinogenicity Tests; Carcinogens; Environmental Exposure; Government Regulation; Guidelines as Topic; Humans; Immunosuppressive Agents; Mice; Models, Biological; Rats; United States
PubMed: 21089807
DOI: No ID Found -
British Medical Journal Dec 1966
Topics: Azathioprine; Chemical Phenomena; Chemistry; Humans
PubMed: 5957425
DOI: No ID Found -
Zeitschrift Fur Gastroenterologie Dec 2014Thiopurines (azathioprine and 6-mercaptopurine) are the most frequently used drugs in the treatment of patients with Crohn's disease. In current guidelines published by... (Review)
Review
Thiopurines (azathioprine and 6-mercaptopurine) are the most frequently used drugs in the treatment of patients with Crohn's disease. In current guidelines published by the German Society of Gastroenterology, Nutritional and Metabolic Diseases (DGVS) in 2014 and by the European Crohn´s and Colitis Organisation (ECCO) in 2010 different indications have been suggested. However, efficacy of azathioprine has been substantially questioned by recent publications in adults as well as in children examining the efficacy of early initiation of this treatment. These articles were published after release of the aforementioned guidelines. Therefore, in this survey recently published data are discussed on the background of our knowledge on the efficacy of azathioprine and 6-mercaptopurine developed in many years, and suggestions for the future use of these substances in the treatment of patients with Crohn's disease will be provided.
Topics: Azathioprine; Crohn Disease; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Practice Guidelines as Topic; Treatment Outcome
PubMed: 25474282
DOI: 10.1055/s-0034-1385650