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The Journal of Clinical Endocrinology... Jan 2024Glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis resulting in tertiary adrenal insufficiency (AI). When weaning patients off glucocorticoids there...
CONTEXT
Glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis resulting in tertiary adrenal insufficiency (AI). When weaning patients off glucocorticoids there is no consensus on whether to maintain patients on prednisolone or convert to hydrocortisone.
OBJECTIVE
Investigate HPA axis recovery in patients on long-term prednisolone and assess outcome after hydrocortisone conversion.
DESIGN
Retrospective cohort study.
SETTING
Outpatient endocrine steroid clinic.
PATIENTS
Patients on long-term prednisolone referred for HPA axis testing between 2015-2022.
MAIN OUTCOMES MEASURED
1) HPA axis recovery rate in patients on prednisolone demonstrated by normal ACTH stimulation test (AST).2) HPA axis recovery rate sub-analysis of dose-matched patients with confirmed tertiary AI on prednisolone or hydrocortisone.
RESULTS
206 patients on prednisolone were tested for tertiary AI. Of these 176 remained on prednisolone while 30 were converted to hydrocortisone. The overall HPA axis recovery rate for patients on prednisolone after interval testing was 137/206 (66.5%). HPA axis recovery rate in dose-matched prednisolone and hydrocortisone conversion groups was 7/10 (70%) and 2/13 (15%) (p=0.008), respectively. There was no difference in mean (SD) age (67.1(12.2) v 63.4(11.1) years; p=0.464) and baseline cortisol (5.3(4.2) v 4.6(3.1)µg/dL; p=0.648) and median [IQR] glucocorticoids duration (1213[1114] v 2316[4808] days; p=0.693) and baseline ACTH (20.5[29.0] v 16.3[14.8]ng/L; p=0.905) between dose-matched prednisolone and hydrocortisone groups. Follow-up duration in prednisolone group was significantly lower (median [IQR] 348[975] v 667[884] days; p=0.012).
CONCLUSIONS
Patients with glucocorticoid induced AI maintained on once-daily prednisolone can recover HPA axis function when weaning. There is no apparent advantage to recover HPA axis function in converting to multiple dosing hydrocortisone.
PubMed: 38298131
DOI: 10.1210/clinem/dgae059 -
International Immunopharmacology Dec 2023Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been...
BACKGROUND
Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies.
OBJECTIVE
Evaluate the long-term efficacy and safety of dupilumab in treating severe BP.
METHODS
Patients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators.
RESULTS
After four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0-3.0) in the D + M group and 10.0 (5.0-12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study.
CONCLUSIONS
Our study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.
Topics: Humans; Pemphigoid, Bullous; Prospective Studies; Antibodies, Monoclonal, Humanized; Methylprednisolone
PubMed: 37925949
DOI: 10.1016/j.intimp.2023.111157 -
BMC Musculoskeletal Disorders Dec 2023Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study...
BACKGROUND
Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD).
METHODS
GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed.
RESULTS
A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted.
CONCLUSION
This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.
Topics: Humans; Intervertebral Disc Degeneration; Intervertebral Disc; Transcription Factors; Autophagy; Methylprednisolone; Glucosamine; Membrane Proteins; Molecular Chaperones; HSP40 Heat-Shock Proteins; Homeodomain Proteins
PubMed: 38041088
DOI: 10.1186/s12891-023-06886-w -
BMJ Open Respiratory Research Aug 2023Interstitial lung abnormalities (ILA) are relatively common incidental findings in participants undergoing low-dose CT screening for lung cancer. Some ILA are transient... (Clinical Trial)
Clinical Trial
INTRODUCTION
Interstitial lung abnormalities (ILA) are relatively common incidental findings in participants undergoing low-dose CT screening for lung cancer. Some ILA are transient and inconsequential, but others represent interstitial lung disease (ILD). Lung cancer screening therefore offers the opportunity of earlier diagnosis and treatment of ILD for some screening participants.
METHODS
The prevalence of ILA in participants in the baseline screening round of the Yorkshire Lung Screening Trial is reported, along with the proportion referred to a regional ILD service, eventual diagnoses, outcomes and treatments.
RESULTS
Of 6650 participants undergoing screening, ILA were reported in 169 (2.5%) participants. Following review in a screening review meeting, 56 participants were referred to the ILD service for further evaluation (0.8% of all screening participants). 2 participants declined referral, 1 is currently awaiting review and the remaining 53 were confirmed as having ILD. Eventual diagnoses were idiopathic pulmonary fibrosis (n=14), respiratory bronchiolitis ILD (n=4), chronic hypersensitivity pneumonitis (n=2), connective tissue disease/rheumatoid arthritis-related ILD (n=4), asbestosis (n=1), idiopathic non-specific interstitial pneumonia (n=1), sarcoidosis (n=1) and pleuroparenchymal fibroelastosis (n=1). Twenty five patients had unclassifiable idiopathic interstitial pneumonia. Overall, 10 people received pharmacotherapy (7 antifibrotics and 3 prednisolone) representing 18% of those referred to the ILD service and 0.15% of those undergoing screening. 32 people remain under surveillance in the ILD service, some of whom may require treatment in future.
DISCUSSION
Lung cancer screening detects clinically significant cases of ILD allowing early commencement of disease-modifying treatment in a proportion of participants. This is the largest screening cohort to report eventual diagnoses and treatments and provides an estimate of the level of clinical activity to be expected by ILD services as lung cancer screening is implemented. Further research is needed to clarify the optimal management of screen-detected ILD.
TRIAL REGISTRATION NUMBER
ISRCTN42704678.
Topics: Humans; Alveolitis, Extrinsic Allergic; Early Detection of Cancer; Idiopathic Pulmonary Fibrosis; Lung; Lung Neoplasms
PubMed: 37612098
DOI: 10.1136/bmjresp-2022-001490 -
Endocrine Connections Jul 2023Patients with adrenal insufficiency (AI) have a higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times....
CONTEXT
Patients with adrenal insufficiency (AI) have a higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times. The cortisol circadian rhythm is difficult to mimic with twice- or thrice-daily hydrocortisone. Prednisolone is a once-daily alternative which may improve patient compliance through its convenience.
OBJECTIVES
Prednisolone day curves can be used to accurately downtitrate patients to the minimum effective dose. This study aimed to review prednisolone day curves and determine therapeutic ranges at different time points after administration.
METHODS
Between August 2013 and May 2021, 108 prednisolone day curves from 76 individuals receiving prednisolone replacement were analysed. Prednisolone concentrations were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. Spearman's correlation coefficient was used to determine the relationship between 2-, 4-, and 6-h prednisolone levels compared to the previously validated standard 8-h prednisolone level (15-25 μg/L).
RESULTS
The median dose was 4 mg of prednisolone once daily. There was a strong correlation between the 4- and 8-h (R = 0.8829, P ≤ 0.0001) and 6- and 8-h prednisolone levels (R = 0.9530, P ≤ 0.0001). Target ranges for prednisolone were 37-62 μg/L at 4 h, 24-39 μg/L at 6 h, and 15-25 μg/L at 8 h. Prednisolone doses were successfully reduced in 21 individuals, and of these, 3 were reduced to 2 mg once daily. All patients were well upon follow-up.
CONCLUSION
This is the largest evaluation of oral prednisolone pharmacokinetics in humans. Low-dose prednisolone of 2-4 mg is safe and effective in most patients with AI. Doses can be titrated with either 4-, 6-, or 8-h single time point drug levels.
PubMed: 37289726
DOI: 10.1530/EC-23-0097 -
Maedica Dec 2023Mesalazine is a drug used to treat ulcerative colitis and Crohn's disease, and is known to rarely cause lung injury. We show herein a unique case who developed this...
Mesalazine is a drug used to treat ulcerative colitis and Crohn's disease, and is known to rarely cause lung injury. We show herein a unique case who developed this drug-induced injury. A 17-year-old boy presented with fever and anorexia after administration of mesalazine. Computed tomography showed extensive ground-glass opacities with peripheral distribution in both lungs. He had general weakness, but had no respiratory symptoms such as cough and dyspnea. With prednisolone, which is primarily aimed at controlling ulcerative colitis, the extensive opacity in both lungs were improved. All patients with this drug-induced lung injury reported to date have had respiratory symptoms, but this patient had no subjective respiratory symptoms and had no abnormalities in respiratory rate and oxyhaemoglobin saturation. Although very rare, we do believe that this clinical course will provide some suggestive information on treatment for patients with similar course in the future.
PubMed: 38348085
DOI: 10.26574/maedica.2023.18.4.718 -
Trials Oct 2023Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are...
Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design.
BACKGROUND
Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen.
METHODS
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients' global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed.
DISCUSSION
This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680.
Topics: Adult; Humans; Colchicine; Prednisolone; Prospective Studies; Arthritis, Gouty; Gout; Pain; Treatment Outcome; Primary Health Care; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37798801
DOI: 10.1186/s13063-023-07666-6 -
Journal For Immunotherapy of Cancer Jul 2023There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
BACKGROUND
There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
METHODS
In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest.
RESULTS
Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death.
CONCLUSIONS
In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP.
TRIAL REGISTRATION NUMBER
jRCT: 1041190029.
Topics: Humans; Prospective Studies; Pneumonia; Prednisolone; Neoplasms; Recurrence
PubMed: 37500182
DOI: 10.1136/jitc-2023-007056 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
ERJ Open Research Sep 2023https://bit.ly/3pR2BSY.
https://bit.ly/3pR2BSY.
PubMed: 37701365
DOI: 10.1183/23120541.00464-2023