Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease.
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ABSTRACT:
SUBMITTER: Gjuladin-Hellon T
PROVIDER: S-EPMC6699648 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6586553 | biostudies-literature
Project description: Not available
| S-EPMC6741529 | biostudies-literature
Project description:Crohn's disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.
| S-EPMC6021420 | biostudies-literature
Project description:Background and aimsThiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy.MethodsUsing the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan-Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the "noncontinuers," we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation.ResultsThe 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ?18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF.ConclusionMost patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization.
| S-EPMC3857068 | biostudies-literature
Project description:The combination therapy of thalidomide and azathioprine (AZA) offers an alternative in clinical practice for Crohn's disease (CD) patients experiencing a loss of response to AZA monotherapy. However, little is known about the efficacy and safety of this combination therapy for patients with CD. This was a retrospective study of 122 consecutive CD patients who lost response to AZA therapy and had switched to a combination therapy of thalidomide and AZA. The primary outcomes were clinical response and clinical remission rates at week 24. Patients who had an initial response to combination therapy were continued on the treatment for remission maintenance. The secondary outcomes were the proportion of clinical relapse throughout maintenance. The Kaplan-Meier method was used to calculate cumulative rates, and Cox regression analysis was used for multivariate analysis. During induction, 80.3% (98/122) patients achieved clinical response within a median duration of 6.5 weeks, (interquartile range, 4.3-8.1 weeks). The rate of clinical remission at 24 weeks was 70.5%. During follow-up, 22.4% (22/98) of the patients that were maintained on combination therapy experienced clinical relapse. The proportions of patients in remission status at 12, 24, and 36 months were 85.1, 78.3, and 70.1%, respectively. Multivariate analysis revealed C-reactive protein >10 mg/L at disease relapse on AZA monotherapy [adjusted hazard ratio (HR), 4.72; 95% CI, 1.19-18.75, P = 0.027] and 6-thioguanine nucleotides level ≥235 pmol/8 × 108 erythrocytes at AZA monotherapy (adjusted HR, 5.32; 95% CI, 1.40-20.14, P = 0.014) were associated with disease relapse on combination therapy. The endoscopic remission rate was 63.6%. Mucosal healing was achieved in 23.6% of the patients. Both Crohn's Disease Endoscopic Index of Severity (13.4 ± 4.92 vs. 6.12 ± 5.24, P < 0.001) and Rutgeerts scores (3.23 ± 0.73 vs. 1.77 ± 1.59, P = 0.003) were significantly decreased with the use of combination therapy. Adverse events occurred in 62 (50.8%) patients, but only 13 (10.7%) necessitated therapy discontinuation. Thalidomide combined with AZA was effective in inducing clinical remission and sustaining long-term steroid-free remission in CD patients who lost response to AZA monotherapy.
| S-EPMC7677527 | biostudies-literature
Project description:AimTo determine the risk factors of nonadherence to azathioprine (AZA) maintenance therapy for Crohn's disease (CD) and to evaluate the influence of patients' educational program on adherence to AZA maintenance therapy.MethodsPatients receiving AZA as maintenance therapy for CD were enrolled. Demographic data, clinical data, and usage information were collected. Univariate and multivariate analyses were performed to identify the risk factors of nonadherence. Then, patients' educational program was conducted. One year after the program, the improvements in adherence and relapse rates were compared between educational and noneducational groups.ResultsA total of 378 CD patients receiving AZA as maintenance therapy were enrolled from September 2008 to September 2018. Nonadherence occurred in 43.9% (166/378) of patients. Univariate analysis revealed that young age, education, alcoholism, anxiety, depression, concern belief, and lack of necessity belief and AZA knowledge were risk factors of nonadherence (P < 0.05). Multivariate logistic regression showed that anxiety (OR 6.244, 95% CI 2.563-15.213), depression (OR 3.801, 95% CI 1.281-11.278), and concern belief (OR 19.531, 95% CI 3.393-120.732) were independent risk factors of nonadherence. Necessity belief (OR 0.961, 95% CI 0.925-0.999) and AZA knowledge (OR 0.823, 95% CI 0.758-0.903) were protective factors of adherence. One year after the AZA educational program, the necessity belief, AZA knowledge, and adherence of the educational group significantly improved (P < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group (P < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, P = 0.035).ConclusionsNonadherence occurred frequently in CD patients receiving AZA maintenance therapy. Educational programs could improve patients' adherence mainly by promoting their beliefs and knowledge of AZA and could reduce relapse rates during treatment.
| S-EPMC7189306 | biostudies-literature
Project description: Not available
| S-EPMC10351211 | biostudies-literature
Project description:ObjectiveThe objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines.BackgroundAzathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist.MethodsClinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed.ResultsTwenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset.ConclusionsNearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.
| S-EPMC5505863 | biostudies-literature
Project description: Not available
| S-EPMC6906134 | biostudies-literature
Project description:The immunosuppressant drug azathioprine is associated with a 4% risk of acute pancreatitis in patients with inflammatory bowel disease (IBD). Studies have demonstrated an increased risk in carriers of HLA-DQA1*02:01 and HLA-DRB1*07:01. We investigated whether these human leukocyte antigen (HLA) types were associated with azathioprine-induced pancreatitis also in Swedish patients with IBD, and whether the type of disease affected the association. Nineteen individuals with IBD who developed acute pancreatitis after initiation of azathioprine were genotyped and compared with a population control cohort (n = 4891) and a control group matched for disease (n = 81). HLA-DQA1*02:01 and HLA-DRB1*07:01 were in full linkage disequilibrium, and were significantly associated with acute pancreatitis both when cases were compared with population controls (OR 3.97 [95% CI 1.57-9.97], p = 0.0035) and matched controls (OR 3.55 [95% CI 1.23-10.98], p = 0.0275). In a disease-specific analysis, the correlation was positive in patients with Crohn's disease versus matched controls (OR 9.27 [95% CI 1.86-46.19], p = 0.0066), but not in those with ulcerative colitis versus matched controls (OR 0.69 [95% CI 0.07-6.74], p = 0.749). In patients with Crohn's disease, we estimated the conditional risk of carriers of HLA-DQA1*02:01-HLA-DRB1*07:01 to 7.3%, and the conditional risk of a non-carrier to 2.2%. We conclude that HLA-DQA1*02:01-HLA-DRB1*07:01 is a marker for increased risk of acute pancreatitis in individuals of Swedish genetic origin, treated with azathioprine for Crohn's disease.
| S-EPMC9099136 | biostudies-literature