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International Journal of Molecular... Nov 2022Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ...
Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ transplantation. The mechanism of action is based on its biologically active metabolite 6-mercaptopurine (6-MP), which is converted, among others, into thioguanine nucleotides capable of incorporating into replicating DNA, which may act as a strong UV chromophore and trigger DNA oxidation. The interaction between azathioprine and DNA, before and after exposure to solar simulator radiation, was investigated using UV-vis spectrometry and differential pulse voltammetry at a glassy carbon electrode. The results indicated that the interaction of AZA with UV radiation was pH-dependent and occurred with the formation of several metabolites, which induced oxidative damage in DNA, and the formation of DNA-metabolite adducts. Moreover, the viability assays obtained for the L929 cell culture showed that both azathioprine and degraded azathioprine induced a decrease in cell proliferation.
Topics: Azathioprine; Photolysis; Mercaptopurine; DNA; Immunosuppressive Agents; DNA Adducts
PubMed: 36430909
DOI: 10.3390/ijms232214438 -
Journal of Gastroenterology Sep 2018Crohn's disease (CD) is a chronic, progressive, and destructive disease of the gastrointestinal tract. Although its incidence appears to be stable or decreasing in most... (Review)
Review
Crohn's disease (CD) is a chronic, progressive, and destructive disease of the gastrointestinal tract. Although its incidence appears to be stable or decreasing in most countries in the North America and Europe, the incidence is rising rapidly in Asian countries. Immunomodulators and biologics are increasingly used to avoid long-term bowel damage and subsequent disability. Therapeutic drug monitoring facilitates optimizing thiopurines and anti-TNFs use. New biologic agents targeting various pathological pathways of CD are blooming in recent years, and the high cost of biologics and expiration of patents for several biologic agents have driven the utility of biosimilars for CD treatment. Here, the literature regarding the efficacy, safety, and withdrawal of the drugs, as well as the evolution of therapeutic targets will be reviewed.
Topics: Adrenal Cortex Hormones; Asia; Azathioprine; Crohn Disease; Drug Monitoring; Humans; Immunomodulation; Immunosuppressive Agents; Incidence; Infliximab; Methotrexate; Purines; Remission Induction; Thalidomide; Thionucleosides; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 29980848
DOI: 10.1007/s00535-018-1479-6 -
Journal of Neurology Jun 2023A variety of novel monoclonal antibodies and immunosuppressant have been proved effective in treating Neuromyelitis Optica Spectrum Disorder (NMOSD). This network... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of novel monoclonal antibodies and immunosuppressant have been proved effective in treating Neuromyelitis Optica Spectrum Disorder (NMOSD). This network meta-analysis compared and ranked the efficacy and tolerability of currently used monoclonal antibodies and immunosuppressive agents in NMOSD.
METHODS
Electronic database including PubMed, Embase and Cochrane Library were searched for relevant studies evaluating monoclonal antibodies and immunosuppressants in patients with NMOSD. The primary outcome measures were annualized relapse rate (ARR), relapse rate, the Expanded Disability Status Scale (EDSS) score, and total adverse events (AEs).
RESULTS
We identified 25 studies with 2919 patients in our meta-analysis. For the primary outcome, rituximab (RTX) (SUCRA: 0.02) ranked first in reduction ARR with a significant difference compared with azathioprine (AZA) (MD - 0.34, 95% CrI - 0.55 to - 0.12) and mycophenolate mofetil (MMF) (MD -0.38, 95% CrI - 0.63 to - 0.14). Tocilizumab (SUCRA: 0.05) ranked first in relapse rate, which was superior to satralizumab (lnOR - 25.4, 95% CrI - 74.4 to - 2.49) and inebilizumab (lnOR - 24.86, 95% CrI - 73.75 to - 1.93). MMF (SUCRA: 0.27) had the fewest AEs followed by RTX (SUCRA: 0.35), both of which showed a significant difference compared with AZA and corticosteroids (MMF vs AZA: lnOR - 1.58, 95% CrI - 2.48 to - 0.68; MMF vs corticosteroids: lnOR - 1.34, 95% CrI - 2.3 to - 0.37) (RTX vs AZA: lnOR - 1.34, 95% CrI - 0.37 to - 2.3; RTX vs corticosteroids: lnOR - 2.52, 95% CrI - 0.32 to - 4.86). In EDSS score, no statistical difference was found between different interventions.
CONCLUSION
RTX and tocilizumab showed better efficacy than traditional immunosuppressants in reducing relapse. For safety, MMF and RTX had fewer AEs. However, studies with larger sample size on newly developed monoclonal antibodies are warranted in the future.
Topics: Humans; Immunosuppressive Agents; Antibodies, Monoclonal; Neuromyelitis Optica; Network Meta-Analysis; Bayes Theorem; Treatment Outcome; Azathioprine; Mycophenolic Acid; Rituximab; Recurrence; Adrenal Cortex Hormones
PubMed: 36884069
DOI: 10.1007/s00415-023-11641-1 -
Bosnian Journal of Basic Medical... Aug 2018The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The... (Review)
Review
The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in CD include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX). Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines only or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of MTX in children suffering from CD. This review summarizes the literature on the therapeutic role of MTX in children with CD. MTX is often administered as a second-line immunomodulator, and 1-year clinical remission was reported in 25-69% of children with CD after excluding for the use of thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first-line immunomodulator in pediatric patients with CD, are promising. A definite conclusion, however, may only be made on the basis of additional research with a larger number of subjects.
Topics: Adolescent; Azathioprine; Child; Crohn Disease; Drug Administration Schedule; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Patient Safety; Remission Induction; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 29338679
DOI: 10.17305/bjbms.2018.2792 -
Current Rheumatology Reports Oct 2023Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies. (Review)
Review
PURPOSE OF REVIEW
Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.
RECENT FINDINGS
Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Kidney; Risk Factors
PubMed: 37452914
DOI: 10.1007/s11926-023-01109-6 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
Saudi Journal of Gastroenterology :... 2022Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it... (Review)
Review
Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it has historically been an important part of pharmacological treatment for patients with inflammatory bowel disease. Despite an increase in therapeutic options, these immunomodulators continue to play important roles in the management of inflammatory bowel disease, used either as a monotherapy in mild to moderate cases or in combination with monoclonal antibodies to prevent immunogenicity and maintain efficacy. In light of data linking the use of thiopurines with the risk of malignancies, methotrexate has regained attention as a potential alternative. In this article, we review data on the pharmacology, safety, and efficacy of methotrexate and discuss options for the positioning of methotrexate alone, or in combination, in therapeutic algorithms for Crohn's disease and ulcerative colitis.
Topics: Azathioprine; Colitis, Ulcerative; Gastroenterologists; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Methotrexate
PubMed: 35042318
DOI: 10.4103/sjg.sjg_496_21 -
Revista Espanola de Enfermedades... May 2021Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting...
Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting diarrhea as a symptom. Herein, we present a patient affected with intractable diarrhea who was transferred to our department. After many laboratory, endoscopy and radiological tests, she was diagnosed with autoimmune enteropathy (AE) and achieved clinical remission with corticosteroids and azathioprine.
Topics: Azathioprine; Diarrhea; Female; Humans; Polyendocrinopathies, Autoimmune
PubMed: 33256418
DOI: 10.17235/reed.2020.7218/2020 -
Annals of the Rheumatic Diseases Nov 2022Previous studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Previous studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of this investigator-initiated study was to compare the efficacy and safety of leflunomide versus azathioprine as maintenance therapy for LN.
METHODS
270 adult patients with biopsy-confirmed active LN from 7 Chinese Rheumatology Centres were enrolled. All patients received induction therapy with 6-9 months of intravenous cyclophosphamide plus glucocorticoids. Patients who achieved complete response (CR) or partial response (PR) were randomised to receive prednisone in combination with leflunomide or azathioprine as maintenance therapy for 36 months. The primary efficacy endpoint was the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects.
RESULTS
A total of 215 patients were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). Kidney flares were observed in 17 (15.7%) leflunomide-treated patients and 19 (17.8%) azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months, p=0.676). 24-hour proteinuria, serum creatinine, serum albumin, serum C3 and serum C4 improved similarly. Extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group. The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%.
CONCLUSIONS
The efficacy and safety profile of leflunomide are non-inferior to azathioprine for maintenance therapy of LN. Leflunomide may provide a new candidate for maintenance therapy in patients with LN.
TRIAL REGISTRATION NUMBER
NCT01172002.
Topics: Adult; Azathioprine; Creatinine; Cyclophosphamide; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunosuppressive Agents; Leflunomide; Lupus Nephritis; Mycophenolic Acid; Prednisone; Prospective Studies; Serum Albumin; Treatment Outcome
PubMed: 35788493
DOI: 10.1136/ard-2022-222486 -
Rheumatic Diseases Clinics of North... Aug 2014Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients... (Review)
Review
Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that the efficacy of mycophenolate mofetil may be similar to that of quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil.
Topics: Azathioprine; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethnopharmacology; Humans; Immunosuppressive Agents; Lupus Nephritis; Medication Therapy Management; Mycophenolic Acid; Organs at Risk; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25034160
DOI: 10.1016/j.rdc.2014.05.001