The association between drugs and repeated treatment with budesonide in patients with microscopic colitis: a retrospective observational study
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PROVIDER: S-EPMC10953108 | biostudies-literature | 2024 Jan
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Project description:BackgroundImmune checkpoint inhibitors (CPIs) are effective against a variety of malignancies but can be limited by inflammatory toxicities such as enterocolitis. Enterocolitis is typically treated with systemically active glucocorticoids. Endoscopy can stratify patients by the severity of mucosal inflammation, including identifying patients with colitis in the absence of visible mucosal changes: microscopic colitis. Whether patients with CPI microscopic colitis could be managed differently from colitis with more severe mucosal involvement is unclear. The objective of this study was to describe outcomes in CPI microscopic colitis focusing on the response to first line treatment with budesonide.MethodsWe evaluated data from a retrospective cohort from a single-center large academic hospital. The participants were all adult patients evaluated by endoscopy for suspected CPI enterocolitis between 3/2017 and 3/2019. The exposures were: Mayo Endoscopic Score (range 0-3). The subset was: oral budesonide, maximum dose 12 mg daily, administered minimum of 5 weeks. The main outcomes and measures were: Primary: time from first CPI exposure to first glucocorticoid use; use of systemic glucocorticoids; time from symptom onset to resolution; continuation of CPI therapy; number of additional CPI infusions received. Secondary: admissions for symptom control; novel irAE development; need for second-line immunosuppression; oncologic outcomes.ResultsWe identified 38 patients with biopsy confirmed CPI enterocolitis, 13 in the microscopic colitis cohort, and 25 in the non-microscopic colitis cohort. Budesonide use was higher in the microscopic colitis cohort (12/13 vs 3/25, p < 0.001), and systemic glucocorticoid use was higher in non-microscopic colitis (22/25 vs. 3/13, p < 0.001). Time from symptom onset to resolution did not differ. Microscopic colitis patients more frequently remained on CPI after developing (entero)colitis (76.9% vs 16.0%, p < 0.001). Microscopic colitis patients tolerating further CPI received, on average, 4.2 CPI infusions more than non-microscopic colitis patients tolerating CPI (5.8 vs 1.6, p = 0.03). Microscopic colitis was associated with increased time-to-treatment-failure (HR 0.30, 95% CI 0.14-0.66) and progression-free survival (HR 0.22, 95% CI 0.07-0.70).ConclusionsGastrointestinal mucosal inflammation without visible mucosal injury is a distinct, prevalent CPI enterocolitis subset that can be diagnosed by endoscopy. First-line budesonide appears effective in controlling "microscopic colitis" symptoms and prolonging immunotherapy duration. These findings present a compelling rationale for routine endoscopic evaluation of suspected CPI enterocolitis and suggest an alternative glucocorticoid-sparing treatment strategy for a subset of such patients.
| S-EPMC6839080 | biostudies-literature
Project description:Background and aimsIncomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi.MethodsPatients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8.ResultsDue to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase.ConclusionsBudesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.
| S-EPMC8435258 | biostudies-literature
Project description:There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81-3.50, I2 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27-2.96, I2 96.46%), NSAIDs (OR 2.02, 95% CI 1.33-2.70, I2 92.70%) and Statins (OR 1.74, 95% CI 1.19-2.30, I2 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32-5.08, I2 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90-6.19, I2 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54-4.92, I2 98.31%), NSAIDs (OR 3.27, 95% CI 2.06-4.48, I2 95.38%), and Statins (OR 2.23, 95% CI 1.41-3.06, I2 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48-0.88, I2 7.26%), (OR 0.46, 95% CI 0.14-0.78, I2 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49-1.42, I2 37.89%), NSAIDs (OR 1.13, 95% CI 0.49-1.76, I2 59.37%) Statins (OR 0.91, 95% 0.66-1.17, I2 0%) and H2RA (OR 3.48, 95% CI -0.41-7.36, I2 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50-1.72, I2 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group.
| S-EPMC9844498 | biostudies-literature
Project description:BackgroundMicroscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce.AimsTo compare clinical characteristics and treatment response by age at diagnosis.MethodsThis retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance.ResultsWe included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m2, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07).ConclusionsThere are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.
| S-EPMC9236988 | biostudies-literature
Project description:IntroductionA study has been developed to assess the use and effectiveness of budesonide MMX for mild-to-moderate active ulcerative colitis (UC) in routine clinical practice.Methods and analysisA prospective, multicentre, observational, cohort study of 300 patients prescribed budesonide MMX for the treatment of mild-to-moderate active UC will be conducted in Europe, Israel and Canada. Patients will be treated with budesonide MMX9 mg daily for induction of remission for ≤8 weeks. Data on effectiveness, including patient-reported outcomes, tolerability and use will be recorded at the end of treatment and at ≥2 weeks after. The primary outcome (improvement ≥3 point in the clinical subscores of the UC Disease Activity Index score at the end of treatment) will be compared in: patients who receive budesonide MMX added to mesalazine >2 weeks after increased/optimised mesalazine dose for the treatment of flare (late add-on); patients who receive budesonide MMX added to mesalazine ≤2 weeks since mesalazine increased/optimised for the treatment of flare, or without mesalazine dose modification (early add-on); and patients who receive budesonide MMX as monotherapy for the treatment of flare (mono). Propensity scoring will be used to minimise bias and confounding inherent in observational studies.Ethics and disseminationFirst ethical approval: Ethikkommission der Ärztekammer Hamburg (12/22/2015). The results will be published in full.DiscussionCompletion of primary data collection is expected in December 2017. Our results will provide further evidence on the effectiveness of budesonide MMX to support clinicians in their daily practice and inform therapeutic guidelines.Trial registration numberNCT02586259.
| S-EPMC4873945 | biostudies-literature
Project description:BackgroundHypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis.MethodsThis retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6-2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis.ResultsAmong 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00-2.84; P = 0.048) after adjusting for several confounding variables.ConclusionsPatients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.
| S-EPMC9685885 | biostudies-literature
Project description:BackgroundUnderstanding and optimising mental health and psychosocial support (MHPSS) interventions in humanitarian crises is crucial, particularly for the most prevalent mental health conditions in conflict settings: anxiety, depression, and post-traumatic stress disorder. However, research on what is the most appropriate length of psychological intervention is lacking in this setting. We aimed to establish which factors are most closely related to improvement and to determine the required number of consultations needed to achieve this improvement.MethodsWe retrospectively analysed records from 9028 patients allocated to treatment for anxiety, depression, and post-traumatic symptoms from the MHPSS programme in Borno State, Nigeria, from January 2018 to December 2019. Patient characteristics, severity (Clinical Global Impression of Severity Scale, CGI-S scale), and clinical improvement were assessed by an attending counsellor (CGI-I scale) and by the patient (Mental Health Global State, MHGS scale). Improvement was defined as scores 1, 2, and 3 in the Clinical Global Impression of Improvement (CGI-I) scale, and as a decrease of at least 4 points in the MHGS scale. We investigated the associations between the category of symptoms, the severity of illness, and improvement of symptoms using multivariable logistic regression. We used Kaplan-Meier (KM) curves to assess the number of consultations (i.e., time of treatment) needed to achieve improvement of symptoms, by symptom category and symptom severity.FindingsThe patients included were referred to treatment for anxiety (n = 3462), depression (n = 3970), or post-traumatic symptoms (n = 1596). Median age was 31 years (range 16-103), and 84.3% were female. Patients categorised as severe were less likely to present improvement according to the CGI-I scale (OR 0.11, 95% CI 0.05-0.25), while none of the other categories of symptoms showed significant results. Overall, three or more consultations were associated with improvement in both scales (OR 3.55, 95% CI 1.47-8.57 for CGI-I; and OR 3.04, 95% CI 2.36-3.90 for MHGS). KM curves for the category of symptoms showed that around 90% of patients with anxiety, depression, or post-traumatic symptoms, as well as those with mild or moderate severity, presented improvement after three consultations, compared with six consultations for those with severe symptoms.InterpretationClassification by severity among patients with anxiety, depression, or post-traumatic symptoms could predict the probability of improvement, whereas classification by symptoms could not. Our study highlights the importance of classifying patient severity in MHPSS programmes to plan and implement the appropriate duration of care. A major limitation was the number of patients lost to follow up after the first consultation and excluded from the logistic regression and KM analysis.FundingThe study was funded and staffed entirely by Médicos Sin Fronteras (Médecins Sans Frontières), Spain.
| S-EPMC10730340 | biostudies-literature
Project description:Ulcerative colitis (UC) is a global, chronic, and refractory disease. Corticosteroids are first-line drugs for the treatment of UC but also cause adverse side effects. Budesonide (BUD), a corticosteroid with relatively low side effects, has been approved by the Food and Drug Administration for use as enteric capsules (Entocort EC) for the treatment of inflammatory bowel disease (IBD). However, this formulation lacks specific targeting ability to UC lesions. Herein, we describe the development of an advanced macrophage-targeted oral lentinan (LNT)-based nanoparticles (NPs) loaded BUD for treatment of UC. Briefly, LNT was used as a food source and natural carrier to load BUD by a simple solvent evaporation method to form LNT/BUD-NPs. LNT showed good loading capacity with high encapsulation and loading efficiencies to BUD of approximately 92.19 and 9.58%, respectively. Evaluation of the gastric stability of LNT/BUD-NPs indicated that LNT could effectively protect BUD from gastric acid and digestive enzymes. The release behavior and transmission electron microscopy image of LNT/BUD-NPs in the intestinal content of mice confirmed that intestinal flora can promote BUD release from LNT. Moreover, evaluation of cellular uptake showed that LNT/BUD-NPs could specifically target macrophages and enhance their uptake rate via the Dectin-1 receptor. In biodistribution studies, LNT/BUD-NPs were able to efficiently accumulate in the inflamed colon of mice. As expected, LNT/BUD-NPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, LNT/BUD-NPs have the advantages of good gastric stability, release mediated by mouse intestinal content, macrophage-targeting, and anti-UC effects. These advantages indicate LNT-based NPs are a promising oral drug delivery system for UC therapy.
| S-EPMC8429481 | biostudies-literature
Project description:Metagenomic sequencing revealed altered microbiota in microscopic colitis
| PRJEB8245 | ENA
Project description:BackgroundMicroscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies.AimsTo determine the association between the use of previously implicated medications and microscopic colitis.MethodsThis was a case-control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non-microscopic colitis controls.ResultsThe study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38-1.13 or nonsteroidal anti-inflammatory drugs, aOR 0.68, 95% CI 0.40-1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17-0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy.ConclusionCompared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis.
| S-EPMC8511165 | biostudies-literature