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Journal of Crohn's & Colitis Jul 2023
Topics: Humans; Mercaptopurine; Colitis, Ulcerative; Azathioprine; Immunosuppressive Agents; Immunologic Factors
PubMed: 37141302
DOI: 10.1093/ecco-jcc/jjad062 -
World Journal of Gastroenterology Dec 2016The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical... (Review)
Review
The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.
Topics: Azathioprine; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; History, 20th Century; History, 21st Century; Humans; Immunosuppressive Agents; Infliximab; Maintenance Chemotherapy; Mercaptopurine; Remission Induction; Tumor Necrosis Factor-alpha
PubMed: 28028358
DOI: 10.3748/wjg.v22.i46.10103 -
Clinical and Experimental Dermatology Feb 2022
Topics: Azathioprine; Dermatology; Genotype; Humans; Methyltransferases; Polymorphism, Genetic
PubMed: 34609021
DOI: 10.1111/ced.14915 -
Journal of Hepatology Aug 2022
Topics: Antibodies, Monoclonal; Azathioprine; Chemical and Drug Induced Liver Injury, Chronic; Humans; Immunosuppressive Agents; Infliximab
PubMed: 35218814
DOI: 10.1016/j.jhep.2022.02.017 -
Liver International : Official Journal... Nov 2020
Topics: Azathioprine; Crohn Disease; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents
PubMed: 32744415
DOI: 10.1111/liv.14615 -
Drugs & Aging Jul 2018Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this... (Review)
Review
Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.
Topics: Age Factors; Azathioprine; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Prednisone
PubMed: 29971609
DOI: 10.1007/s40266-018-0556-0 -
Zeitschrift Fur Rheumatologie Feb 2024This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies for lupus nephritis.
METHODS
Randomized controlled trials (RCTs) examining the efficacy and safety of CNI, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs.
RESULTS
Ten RCTs comprising 884 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (odds ratio [OR] 0.72, 95% credible interval [CrI] 0.45-1.22). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.85, 95% CrI 0.34-2.00). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by CNI and AZA. The incidence of leukopenia in the MMF and CNI groups was significantly lower than that in the AZA group (OR 0.12, 95% CrI 0.04-0.34; OR 0.16, 95% CrI 0.04-0.50; respectively). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawals due to adverse events showed a similar pattern.
CONCLUSION
Lower relapse rates combined with a more favorable safety profile suggest that CNI and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.
Topics: Humans; Azathioprine; Mycophenolic Acid; Lupus Nephritis; Immunosuppressive Agents; Calcineurin Inhibitors; Network Meta-Analysis; Treatment Outcome; Recurrence
PubMed: 37278824
DOI: 10.1007/s00393-023-01374-x -
Clinical Pharmacology and Therapeutics Jan 2022Azathioprine is used frequently to treat several inflammatory conditions. However, treatment is limited by adverse events-in particular, myelotoxicity....
Azathioprine is used frequently to treat several inflammatory conditions. However, treatment is limited by adverse events-in particular, myelotoxicity. Thiopurine-S-methyltransferase (TPMT) and nudix hydrolase-15 (NUDT15) are enzymes involved in azathioprine metabolism; variants in the genes encoding these enzymes increase the risk for azathioprine myelotoxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended dose adjustments based on the results of TPMT and NUDT15 genotyping. However, little is known about the importance of this genetic information in routine clinical care. We hypothesized that in patients with inflammatory diseases, TPMT and NUDT15 genotype data predict the risk of discontinuing azathioprine due to myelotoxicity. This was a retrospective cohort study in 1,403 new adult azathioprine users for the management of inflammatory conditions for whom we had genetic information and clinical data. Among patients who discontinued azathioprine, we adjudicated the reason(s). Genotyping was performed using the Illumina Infinium Expanded Multi-Ethnic Genotyping Array plus custom content. We used CPIC guidelines to determine TPMT and NUDT15 metabolizer status; patients were grouped as either: (i) poor/intermediate, or (ii) normal/indeterminate metabolizers. We classified 110 patients as poor/intermediate, and 1,293 patients as normal/indeterminate metabolizers. Poor/intermediate status was associated with a higher risk for azathioprine discontinuation due to myelotoxicity compared to normal/indeterminate metabolizers (hazard ratio (HR) = 2.90, 95% confidence interval (CI): 1.58-5.31, P = 0.001). This association remained significant after adjustment for race, age at initiation, sex, primary indication, and initial daily dose of azathioprine (adjusted HR (aHR) = 2.67, 95% CI: 1.44-4.94, P = 0.002). In conclusion, TPMT and NUDT15 metabolizer status predicts discontinuation due to myelotoxicity for patients taking azathioprine for inflammatory conditions.
Topics: Adult; Anti-Inflammatory Agents; Azathioprine; Bone Marrow Diseases; Cohort Studies; Female; Humans; Inflammation; Male; Methyltransferases; Middle Aged; Odds Ratio; Pharmacogenetics; Pharmacogenomic Variants; Polymorphism, Genetic; Probability; Pyrophosphatases; Retrospective Studies
PubMed: 34582038
DOI: 10.1002/cpt.2428 -
The Journal of Allergy and Clinical... Mar 2019Azathioprine hypersensitivity syndrome is a rare complication of azathioprine therapy. Its symptoms resemble infection or relapse of inflammatory disease, hindering... (Observational Study)
Observational Study
BACKGROUND
Azathioprine hypersensitivity syndrome is a rare complication of azathioprine therapy. Its symptoms resemble infection or relapse of inflammatory disease, hindering correct diagnosis. Current literature is limited to sporadic case reports and reviews.
OBJECTIVE
To estimate the incidence of azathioprine hypersensitivity syndrome and describe its characteristics in the context of an observational cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Also, to facilitate early recognition and awareness among clinicians.
METHODS
Within a cohort of 290 patients with ANCA-associated vasculitis receiving azathioprine maintenance therapy, frequency of azathioprine hypersensitivity was described and characteristics were compared between hypersensitive and nonhypersensitive patients. Clinical picture, laboratory abnormalities, and concurrent medication of patients with azathioprine hypersensitivity were described.
RESULTS
Of 290 patients, 25 (9%) experienced azathioprine hypersensitivity after a median of 14 (interquartile range [IQR] 12-18) days. Frequent symptoms were fever (100%), malaise (60%), arthralgia (36%), and rash (32%). All patients used prednisolone (median 10 mg/day, IQR 9.4-16.3 mg/day) at the time of the hypersensitivity reaction. Most patients had a rise in C-reactive protein (CRP), leukocyte counts, and neutrophil counts, but no eosinophilia. Thiopurine S-methyltransferase (TPMT) activity was significantly lower in hypersensitive patients (median 74.4 [IQR 58.0-80.1] nmol/gHb/L) compared with controls (median 81.4 [71.9-90.5] nmol/gHb/L), P = .01. Hypersensitive patients had a higher risk of relapse (hazard ratio 2.2, 95% confidence interval 1.2-4.2; P = .01).
CONCLUSIONS
Azathioprine hypersensitivity syndrome is strikingly common in ANCA-associated vasculitis, might be associated with reduced TPMT activity, is accompanied by an increase in neutrophil counts, and may occur even during concomitant prednisolone therapy. Proper recognition may prevent unnecessary hospital procedures and damage to the patient.
Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Azathioprine; Drug Hypersensitivity; Female; Fever; Humans; Male; Middle Aged
PubMed: 30368003
DOI: 10.1016/j.jaip.2018.10.018 -
Cellular and Molecular Biology... Feb 2022Fenbfen is used for pain, pyrexia and in the management of osteoarthritis, rheumatoid arthritis and other musculoskeletal disorders. The present research was planned to...
Fenbfen is used for pain, pyrexia and in the management of osteoarthritis, rheumatoid arthritis and other musculoskeletal disorders. The present research was planned to examine the immunomodulatory activity of fenbufen in different models of cell-mediated immunity (CMI) and humoral immunity (HI). The CMI was evaluated by delayed-type hypersensitivity (DTH) and cyclophosphamide-induced neutropenia assays while HI was appraised by hemagglutination (HA) assay by administering fenbufen at 2, 6 and 10 mg.kg-1 and azathioprine 40 mg.kg-1 (as standard therapy) to albino mice by intraperitoneal route. The ex vivo immunomodulatory action was determined by red blood cell (RBC) membrane stabilization and protein denaturation assays. The results showed that fenbufen treatment had significantly (p<0.05-p<0.001) reduced white blood cells, hemoglobin content, and red blood cells in the healthy and neutropenic mice. A significant (p<0.001) reduction in activities of superoxide dismutase and catalase and glutathione contents, and enhancement of malondialdehyde level were observed in neutropenic mice that were restored by fenbufen treatment. It suppressed DTH reaction after 24, 48 and 72 h post topical application of 2, 4-dinitrofluorobenzene (DNFB). Fenbufen or azathioprine treated groups also showed a significant reduction in the antibody titer against human RBCs induced immune activation in mice as compared to the disease control mice. Fenbufen showed IC50 of 14.0, 50.5 and 66.2 μg.ml-1 whereas, diclofenac sodium showed IC50 of 61.0, 126 and 50.5 μg/ml in RBCs membrane stabilization, egg albumin and bovine serum albumin denaturation assays respectively. The current study shows that fenbufen might have potential immunomodulatory activity against CMI and HI. It can be utilized to treat immune system disorders.
Topics: Animals; Azathioprine; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunity, Humoral; Mice; Phenylbutyrates
PubMed: 35818275
DOI: 10.14715/cmb/2021.67.5.4