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Internal Medicine (Tokyo, Japan) 2012
Topics: Azathioprine; Hepatitis, Viral, Human; Humans; Immunosuppressive Agents; Male; Prednisolone
PubMed: 22892481
DOI: 10.2169/internalmedicine.51.8197 -
Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
Arthritis Care & Research Sep 2022Underrepresented racial and ethnic minorities are disproportionately affected by systemic lupus erythematosus (SLE). Racial and ethnic minorities also have more severe...
OBJECTIVE
Underrepresented racial and ethnic minorities are disproportionately affected by systemic lupus erythematosus (SLE). Racial and ethnic minorities also have more severe SLE manifestations that require use of immunosuppressive medications, and often have lower rates of medication adherence. We aimed to explore barriers of adherence to SLE immunosuppressive medications among minority SLE patients.
METHODS
We conducted a qualitative descriptive study using in-depth interviews with a purposive sample of racial minority SLE patients taking oral immunosuppressants (methotrexate, azathioprine, or mycophenolate), and lupus clinic providers and staff. Interviews were audiorecorded, transcribed, and analyzed using applied thematic analysis. We grouped themes using the Capability, Opportunity, Motivation, Behavior conceptual model.
RESULTS
We interviewed 12 SLE patients (4 adherent, 8 nonadherent) and 12 providers and staff. We identified capability barriers to include external factors related to acquiring medications, specifically cost-, pharmacy-, and clinic-related issues; opportunity barriers to include external barriers to taking medications, specifically logistic- and medication-related issues; and motivation factors to include intrinsic barriers, encompassing patients' knowledge, beliefs, attitudes, and physical and mental health. The most frequently described barriers were cost, side effects, busyness/forgetting, and lack of understanding, although barriers differed by patient and adherence level, with logistic and intrinsic barriers described predominantly by nonadherent patients and side effects described predominantly by adherent patients.
CONCLUSION
Our findings suggest that interventions may be most impactful if they are designed to facilitate logistics of taking medications and increase patients' motivation while allowing for personalization to address the individual differences in adherence barriers.
Topics: Azathioprine; Ethnic and Racial Minorities; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Qualitative Research
PubMed: 33662174
DOI: 10.1002/acr.24591 -
Indian Pediatrics Jan 2019Idiopathic pulmonary hemosiderosis is conventionally treated with steroids, prolonged usage of which maybe deleterious and disease often recurs on tapering. We initiated...
Idiopathic pulmonary hemosiderosis is conventionally treated with steroids, prolonged usage of which maybe deleterious and disease often recurs on tapering. We initiated hydroxy-chloroquine and azathioprine early in treatment along with steroids in seven children with idiopathic pulmonary hemosiderosis, and observed that early introduction of second line immunosuppressants helped in reducing disease flare and steroid toxicity without serious adverse effects.
Topics: Azathioprine; Child; Hemosiderosis; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lung Diseases; Time-to-Treatment; Hemosiderosis, Pulmonary
PubMed: 30806370
DOI: No ID Found -
Journal of Pediatric Gastroenterology... Jul 2017Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target...
OBJECTIVES
Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission.
METHODS
A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected.
RESULTS
Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ± 5.1 years) with a mean follow-up period of 2.9 ± 3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2 ± 9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8 × 10 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ≤50 U/L).
CONCLUSIONS
The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
Topics: Adolescent; Azathioprine; Biomarkers; Child; Child, Preschool; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Male; Retrospective Studies; Thioguanine; Treatment Outcome
PubMed: 28272159
DOI: 10.1097/MPG.0000000000001563 -
Medicina (Kaunas, Lithuania) Aug 2019In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a...
In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. In the entire cohort, only 8 cases of heterozygous mutations of TPMT were observed, corresponding to 4% mutated haplotype rate, much lower than that reported in literature (close to 10%). No homozygous mutation was found. Regarding the TPMT allelic variants, we did not find any statistically significant difference between patients who tolerated azathioprine and those who suffered from adverse events. (OR = 0.77, 95% CI = 0.08-7.72; = 0.82). According to our study, in IBD patients, the search for TPMT gene mutations before starting treatment with azathioprine is not helpful in predicting the occurrence of adverse events. Importantly, patients with allelic variants should not be denied the therapeutic option of azathioprine, as they may tolerate this drug.
Topics: Adolescent; Adult; Aged; Azathioprine; Female; Genotype; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Methyltransferases; Middle Aged
PubMed: 31387318
DOI: 10.3390/medicina55080441 -
Redox Report : Communications in Free... Dec 2021Crohn's disease (CD) is a chronic inflammatory disease without a specific cause. Inflammation in these patients can disturb the oxidants/antioxidants balance and results...
BACKGROUND
Crohn's disease (CD) is a chronic inflammatory disease without a specific cause. Inflammation in these patients can disturb the oxidants/antioxidants balance and results in oxidative stress that plays a destructive role. This study aimed to evaluate the gene expression of , , , and in CD patients before and after Azathioprine (Aza) consumption.
METHOD
Peripheral bloodmononuclear cells (PBMCs) were separated from CD patients (= 15, mean age = 33.6 ± 1.8) before and after treatment with Aza and healthy controls (= 15, mean age = 31.5 ± 1.2). The expression levels of , , , and were measured in byusing real-time qRT-PCR technique.
RESULT
The expression levels of (value < 0.001), (value < 0.05), (-value < 0.001), (-value < 0.001) were significantly increased compared to control group. Following treatment with Aza, the decreased expression levels of (value < 0.05), (value < 0.05), (-value < 0.001) and (-value < 0.001) were observed in CD patients.
CONCLUSION
Overall, our results showed that prescription of Azathioprine can lead to the altered expression of redox system-related genes in patients with CD.
Topics: Antioxidants; Azathioprine; Crohn Disease; Humans; Oxidation-Reduction; Oxidative Stress
PubMed: 33882797
DOI: 10.1080/13510002.2021.1915665 -
Alimentary Pharmacology & Therapeutics Oct 2002The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial. (Clinical Trial)
Clinical Trial Comparative Study
Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission.
BACKGROUND
The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial.
AIM
To evaluate the efficacy and tolerability of these two drugs in a series of patients with steroid-dependent or steroid-resistant active ulcerative colitis.
METHODS
Forty-two patients were treated with a daily dose of azathioprine (2 mg/kg) and, if intolerant or not responding, with methotrexate (12.5 mg/week intramuscularly), and their efficacy was established by clinical, endoscopic and histological examinations at 6 months. Patients achieving clinical remission continued with treatment and were followed up.
RESULTS
Of the 42 patients on azathioprine, 10 experienced early side-effects requiring withdrawal from treatment, 22 (69%) achieved complete remission, six (19%) achieved improvement and four (12%) obtained no substantial benefit. Methotrexate, administered to eight patients intolerant to and two patients resistant to azathioprine, induced complete remission in six patients (60%) and improvement in four (40%). During follow-up, a larger number of patients on azathioprine relapsed in comparison with patients on methotrexate [16/28 (57%) vs. 2/10 (20%), respectively; P < 0.05]. Only minor side-effects were observed on both treatments.
CONCLUSIONS
Azathioprine is effective in patients with steroid-dependent or steroid-resistant ulcerative colitis. Methotrexate seems to be a good alternative in patients intolerant to or not responding to azathioprine.
Topics: Adult; Aged; Anti-Inflammatory Agents; Azathioprine; Colitis, Ulcerative; Drug Administration Schedule; Drug Resistance; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Single-Blind Method; Treatment Outcome
PubMed: 12269968
DOI: 10.1046/j.1365-2036.2002.01340.x -
Pharmacology Research & Perspectives May 2021Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine...
Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6-mercaptopurine (6-MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine-induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6-MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu-like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu-like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine-induced toxicity.
Topics: Adolescent; Adult; Aged; Asian People; Azathioprine; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Leukopenia; Male; Mercaptopurine; Middle Aged; Retrospective Studies; Xanthine Oxidase; Young Adult
PubMed: 33929082
DOI: 10.1002/prp2.764 -
European Journal of Pediatrics Aug 2022To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral...
To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI) > 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score < 3 without treatment escalation at week 10. Secondary outcomes included proportion of patients without treatment escalation at week 52. In total, 27/47 patients received EEN and 20/47 corticosteroids. At baseline, patient demographics and several inflammation parameters were similar between the two treatment groups. At 10 weeks, clinical remission rates were 7/23 (30%) for EEN and 7/19 (37%) for corticosteroids (p = 0.661). Twenty-nine of 47 consented to endoscopy at 10 weeks, showing endoscopic remission rates without treatment escalation in 2/16 (13%) of EEN-treated patients and in 1/13 (8%) of corticosteroid-treated patients (p = 1.00). At week 52, 23/27 (85%) EEN-treated patients received treatment escalation (median 14 weeks) and 13/20 (65%) corticosteroid-treated patients (median 27 weeks), p = 0.070.Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10. Trial registration number: NCT02517684 What is Known: • Endoscopic remission is associated with a low risk of disease progression. • FL-IFX was superior to conventional treatment in achieving and maintaining remission in paediatric patients with moderate-to-severe CD the first year from diagnosis. What is New: • In children with newly diagnosed moderate-to-severe CD, clinical remission rates and endoscopic remission rates without treatment escalation at week 10 were 30% and 13% after EEN and 37% and 8% after corticosteroid induction treatment. • The current treatment target was often not achieved by either EEN or corticosteroid induction treatment after bridging to azathioprine.
Topics: Adrenal Cortex Hormones; Azathioprine; Child; Crohn Disease; Enteral Nutrition; Humans; Remission Induction; Treatment Outcome
PubMed: 35672586
DOI: 10.1007/s00431-022-04496-7