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Kidney International Feb 2023The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the... (Randomized Controlled Trial)
Randomized Controlled Trial
Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy.
The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study.
Topics: Adult; Humans; Budesonide; Double-Blind Method; Glomerular Filtration Rate; Glomerulonephritis, IGA; Kidney Function Tests; Treatment Outcome
PubMed: 36270561
DOI: 10.1016/j.kint.2022.09.017 -
Gastroenterologia Y Hepatologia 2018Oral budesonide is a glucocorticoid of primarily local action. In the field of digestive diseases, it is used mainly in inflammatory bowel disease, but also in other... (Review)
Review
Oral budesonide is a glucocorticoid of primarily local action. In the field of digestive diseases, it is used mainly in inflammatory bowel disease, but also in other indications. This review addresses the pharmacology, pharmacodynamics and therapeutic use of budesonide. Its approved indications are reviewed, as well as other clinical scenarios in which it could play a role, in order to facilitate its use and improve the accuracy of its prescription.
Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Controlled Clinical Trials as Topic; Crohn Disease; Humans; Ileostomy; Postoperative Complications; Practice Guidelines as Topic
PubMed: 30007787
DOI: 10.1016/j.gastrohep.2018.05.013 -
Revista Espanola de Enfermedades... Jan 2020Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes:... (Review)
Review
Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antidiarrheals; Antimetabolites; Azathioprine; Biological Products; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Diarrhea; Humans; Loperamide; Malabsorption Syndromes; Mesalamine; Methotrexate; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Time Factors
PubMed: 31880163
DOI: 10.17235/reed.2019.6655/2019 -
The Journal of Allergy and Clinical... Mar 2023The Global Initiative for Asthma recommends that low-dose inhaled corticosteroid (ICS)/formoterol be preferred to short-acting beta-agonists as reliever therapy in... (Review)
Review
The Global Initiative for Asthma recommends that low-dose inhaled corticosteroid (ICS)/formoterol be preferred to short-acting beta-agonists as reliever therapy in adolescents and adults with asthma, across the range of asthma severity. This recommendation represents the most fundamental change in asthma management for many decades. In this commentary, we review the rationale for combination ICS/formoterol therapy, the evidence on which this recommendation has been made, the limitations in the evidence, the practical issues relevant to the implementation of ICS/formoterol reliever-based regimens in clinical practice, and the emerging evidence for the efficacy and safety of combination ICS/salbutamol reliever therapy regimens.
Topics: Adult; Adolescent; Humans; Formoterol Fumarate; Budesonide; Bronchodilator Agents; Anti-Asthmatic Agents; Asthma; Adrenal Cortex Hormones; Drug Therapy, Combination; Administration, Inhalation; Ethanolamines
PubMed: 36639054
DOI: 10.1016/j.jaip.2023.01.002 -
Hepatology (Baltimore, Md.) Apr 2023In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or...
BACKGROUND AND AIMS
In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options.
APPROACH AND RESULTS
This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047).
CONCLUSIONS
In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.
Topics: Humans; Budesonide; Prednisone; Hepatitis, Autoimmune; Retrospective Studies; Glucocorticoids
PubMed: 36626622
DOI: 10.1097/HEP.0000000000000018 -
Respiratory Research Oct 2022Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.
METHODS
Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.
RESULTS
The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).
CONCLUSIONS
Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Antitussive Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Capsaicin; Cough; Cyclopropanes; Formoterol Fumarate; Humans; Inflammation; Leukotriene Antagonists; Quinolines; Sulfides
PubMed: 36217131
DOI: 10.1186/s12931-022-02114-6 -
JAMA Network Open Mar 2022The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever.
OBJECTIVE
To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma.
DATA SOURCES
For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever.
STUDY SELECTION
Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher.
DATA EXTRACTION AND SYNTHESIS
Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021.
MAIN OUTCOMES AND MEASURES
The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression.
RESULTS
Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.
Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Female; Formoterol Fumarate; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 35230437
DOI: 10.1001/jamanetworkopen.2022.0615 -
Advances in Therapy May 2022Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a... (Review)
Review
Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a long-acting bronchodilator, depending on asthma severity, and may also be supplemented with short-acting bronchodilators for as-needed rescue medication. Adherence to asthma therapies is generally poor and characterized by underuse of ICS therapies and over-reliance on short-acting bronchodilators, which leads to poor clinical outcomes. This article reviews efficacy versus systemic activity profiles for various dosing regimens of budesonide (BUD) and fluticasone propionate (FP). We performed a structured literature review of BUD and FP regular daily dosing, and BUD/formoterol (FOR) as-needed dosing, to explore the relationship between various dosing patterns of ICS regimens and the risk-benefit profile in terms of the extent of bronchoprotection and cortisol suppression. In addition, we explored how adherence could potentially affect the risk-benefit profile, in patients with mild, moderate, and moderate-to-severe asthma. With a specific focus on BUD or FP-containing treatments, we found that regular daily ICS and ICS/long-acting β-agonist (LABA) dosing had a greater degree of bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR maintenance and reliever therapy (MART) dosing, and still maintained low systemic activity. We also found that the benefits of regular daily ICS dosing regimens were diminished when adherence was low (50%); the shorter duration of bronchoprotection observed was similar to that seen with typical as-needed BUD/FOR usage. These findings have implications for aiding clinicians with selecting the most suitable treatment option for asthma management, and subsequent implications for the advice clinicians give their patients.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans
PubMed: 35284999
DOI: 10.1007/s12325-022-02092-7 -
BMJ Open Respiratory Research Dec 2021Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study.
INTRODUCTION
Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.
METHODS AND ANALYSIS
The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.
ETHICS AND DISSEMINATION
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.
TRIAL REGISTRATION
NCT03769090.
Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans
PubMed: 34887317
DOI: 10.1136/bmjresp-2021-001077 -
BMJ Clinical Evidence Mar 2009Croup leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects... (Review)
Review
INTRODUCTION
Croup leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects about 3% of children a year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by Parainfluenza virus. Symptoms usually resolve within 48 hours, but severe infection can, rarely, lead to pneumonia, and to respiratory failure and arrest.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in children with: mild croup; moderate to severe croup; and impending respiratory failure because of severe croup? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, dexamethasone (intramuscular, oral, single-dose oral, route of administration), heliox, humidification, intermittent positive pressure breathing, L-adrenaline, nebulised adrenaline (epinephrine), nebulised budesonide, nebulised short-acting beta(2) agonists, oral decongestants, oral prednisolone, oxygen, and sedatives.
Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Budesonide; Croup; Dexamethasone; Epinephrine; Humans; Infant
PubMed: 19445760
DOI: No ID Found