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The Journal of International Medical... Mar 2023IgG-4-related autoimmune hepatitis (IgG4-AIH) is a rare disease. We report here a case of IgG4-AIH in an elderly male patient who was admitted to hospital because of...
IgG-4-related autoimmune hepatitis (IgG4-AIH) is a rare disease. We report here a case of IgG4-AIH in an elderly male patient who was admitted to hospital because of unexplained hepatic insufficiency. After excluding viral hepatitis, alcoholic liver disease, drug-induced liver disease, parasitic infection, hepatolenticular degeneration and other diseases, and observing elevated levels of IgG-4, humoral immunity index, abnormal liver disease antibody spectrum and liver biopsy results, we made a diagnosis of IgG4-AIH. Following treatment with prednisone and ursodeoxycholic acid, the patient's liver function improved significantly and the patient was discharged from hospital.
Topics: Humans; Male; Aged; Hepatitis, Autoimmune; Immunoglobulin G; Prednisone; Hepatolenticular Degeneration; Liver Failure
PubMed: 36999654
DOI: 10.1177/03000605231164003 -
Respiratory Medicine May 2018
Topics: Humans; Prednisone; Sarcoidosis; Sarcoidosis, Pulmonary; Steroids
PubMed: 29276075
DOI: 10.1016/j.rmed.2017.12.009 -
Arthritis Research & Therapy Feb 2024Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to...
BACKGROUND
Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis.
METHODS
Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day.
RESULTS
Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (OR = 3.71 [95%CI = 1.34-10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (OR = 2.61 [95%CI = 1.07-6.41]; p = 0.036), lower chronicity index (OR 1.33 per unit decrease [95%CI = 1.10-1.62]; p = 0.003), and positive anti-dsDNA antibody (OR = 2.61 [95%CI = 0.93-7.33]; p = 0.069).
CONCLUSIONS
CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Prospective Studies; Creatinine; Prednisone; Treatment Outcome; Remission Induction; Retrospective Studies; Kidney
PubMed: 38378664
DOI: 10.1186/s13075-024-03275-z -
Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis.Aging and Disease Apr 2024Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy...
Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p < 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p < 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p < 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p < 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.
Topics: Humans; Receptors, Cholinergic; Prednisone; Activities of Daily Living; Prospective Studies; Myasthenia Gravis; Antibodies, Monoclonal, Humanized
PubMed: 37450932
DOI: 10.14336/AD.2023.0528 -
Cell Communication and Signaling : CCS Jun 2022Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the...
BACKGROUND
Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH.
METHODS
Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin-eosin staining to determine the role of gut microbiota on AIH.
RESULTS
Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner.
CONCLUSION
Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH. Video Abstract.
Topics: Animals; Gastrointestinal Microbiome; Hepatitis, Autoimmune; Humans; Lactobacillus; Leukocytes, Mononuclear; Mice; Prednisone; T Follicular Helper Cells
PubMed: 35658901
DOI: 10.1186/s12964-021-00819-7 -
Frontiers in Immunology 2022Two clinical trials assessing the steroid-sparing effect of methotrexate (MTX) yielded conflicting results. Our objective was to investigate whether MTX would show a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Two clinical trials assessing the steroid-sparing effect of methotrexate (MTX) yielded conflicting results. Our objective was to investigate whether MTX would show a steroid-sparing effect in the treatment of generalized myasthenia gravis (MG) patients who fitted Myasthenia Gravis Foundation of America (MGFA) Class II and Class III.
METHODS
We performed an 18-month prospective, randomized, open-labeled trial of prednisone combined with MTX 10 mg orally every week versus prednisone alone in 40 recently diagnosed MG patients of MGFA Class II and Class III between July 2014 and July 2018. The primary endpoint was the prednisone area under the dose-time curve (AUDTC) from months 3 to 18. Secondary endpoints included changes of the Quantitative Myasthenia Gravis Score (QMG), the Myasthenia Gravis Activity of Daily Living Score (MG-ADL), initial time of prednisone reduction, the median prednisone daily dose in each month, adverse events, and treatment failures in each group.
RESULTS
Forty participants were included; among those, 5 individuals withdrew. A total of 35 participants completed 18 months of follow-up (18 in prednisone+MTX, 17 in prednisone group). Combined use of MTX reduced the month 3-18 prednisone AUDTC (prednisone+MTX 5,663.44 ± 1,678.08 mg, prednisone 6,683.94 ± 678.08 mg, = 0.03, 95% confidence interval -1916.01 to -124.98). The initial times of prednisone reduction were 4.34 ± 1.44 months in the prednisone+MTX group and 5.56 ± 2.05 months in the prednisone group ( = 0.04, 95% CI -2.41 to -0.03). The median daily prednisone dose was significantly lower in the prednisone+MTX group at month 6 and months 9-18. No significant differences were found in QMG and MG-ADL scores between the two groups. No serious drug-related adverse events were observed in both groups.
CONCLUSIONS
This study provides evidence that MTX has the steroid-sparing ability in generalized MG patients of MGFA Class II and Class III.
CLINICAL TRIAL REGISTRATION
http://www.chictr.org.cn/showproj.aspx?proj=10563 identifier ChiCTR-IPR-15006081.
Topics: Area Under Curve; Humans; Methotrexate; Myasthenia Gravis; Prednisone; Prospective Studies
PubMed: 35371086
DOI: 10.3389/fimmu.2022.839075 -
The Oncologist Dec 2014Abiraterone acetate, a prodrug of the CYP17A1 inhibitor abiraterone that blocks androgen biosynthesis, is approved for treatment of patients with metastatic... (Review)
Review
Abiraterone acetate, a prodrug of the CYP17A1 inhibitor abiraterone that blocks androgen biosynthesis, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone or prednisolone 5 mg twice daily. This review evaluates the basis for the effects of prednisone on mineralocorticoid-related adverse events that arise because of CYP17A1 inhibition with abiraterone. Coadministration with the recommended dose of glucocorticoid compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in adrenocorticotropic hormone seen with abiraterone. Consequently, 5 mg prednisone twice daily serves as a glucocorticoid replacement therapy when coadministered with abiraterone acetate, analogous to use of glucocorticoid replacement therapy for certain endocrine disorders. We searched PubMed to identify safety concerns regarding glucocorticoid use, placing a focus on longitudinal studies in autoimmune and inflammatory diseases and cancer. In general, glucocorticoid-related adverse events, including bone loss, immunosuppression, hyperglycemia, mood and cognitive alterations, and myopathy, appear dose related and tend to occur at doses and/or treatment durations greater than the low dose of glucocorticoid approved in combination with abiraterone acetate for the treatment of mCRPC. Although glucocorticoids are often used to manage tumor-related symptoms or to prevent treatment-related toxicity, available evidence suggests that prednisone and dexamethasone might also offer modest therapeutic benefit in mCRPC. Given recent improvements in survival achieved for mCRPC with novel agents in combination with prednisone, the risks of these recommended glucocorticoid doses must be balanced with the benefits shown for these regimens.
Topics: Androstenes; Antineoplastic Agents, Hormonal; Disease Progression; Humans; Male; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms, Castration-Resistant
PubMed: 25361624
DOI: 10.1634/theoncologist.2014-0167 -
Journal of Neuromuscular Diseases 2023Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited.
BACKGROUND
Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited.
OBJECTIVE
Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD.
METHODS
Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models.
RESULTS
This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids).
CONCLUSIONS
Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.
Topics: Male; Humans; Adolescent; Prednisone; Stroke Volume; Longitudinal Studies; Quality of Life; Ventricular Function, Left; Muscular Dystrophy, Duchenne; Disease Progression
PubMed: 36565131
DOI: 10.3233/JND-221575 -
The Cochrane Database of Systematic... Aug 2015Optic neuritis is an inflammatory disease of the optic nerve. It usually presents with an abrupt loss of vision and recovery of vision is almost never complete. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optic neuritis is an inflammatory disease of the optic nerve. It usually presents with an abrupt loss of vision and recovery of vision is almost never complete. It occurs more commonly in women than in men. Closely linked in pathogenesis, optic neuritis may be the initial manifestation for multiple sclerosis. In some people, no underlying cause can be found.
OBJECTIVES
The objective of this review was to assess the effects of corticosteroids on visual recovery in eyes with acute optic neuritis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2015, Issue 4), MEDLINE (January 1950 to April 2015), EMBASE (January 1980 to April 2015), Latin American and Caribbean Health Sciences Literature (LILACS) (January 1982 to April 2015), PubMed (January 1946 to April 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The metaRegister of Controlled Trials (mRCT) was last searched on 6 March 2014. The electronic databases were last searched on 7 April 2015. We also searched reference lists of identified trial reports for additional trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that evaluated systemic corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs with a total of 750 participants. Each trial was conducted in a different country: Denmark, Germany, India, Japan, UK, and United States. Additionally, we identified two ongoing trials not due to be completed until 2016. Among the six trials included in this review, we judged one to be at high risk of bias. The remaining five trials were judged to be at either low or uncertain risk of biases.Five trials compared only two intervention groups and one trial had a three-arm comparison of oral corticosteroids or intravenous corticosteroids with placebo. Of the five trials with only two intervention groups, two trials compared oral corticosteroids versus placebo, two trials compared intravenous corticosteroids with placebo, and one trial compared intravenous dexamethasone with intravenous methylprednisolone plus oral prednisolone.Three trials evaluating oral corticosteroids used varying doses of corticosteroids versus placebo. In the meta-analyses to assess visual acuity, the risk ratio (RR) was 1.00 (95% confidence interval (CI) 0.82 to 1.23; participants = 398) at one month; 0.92 (95% CI 0.77 to 1.11; participants = 355) at six months; and 0.93 (95% CI 0.70 to 1.24; participants = 368) at one year. In the meta-analyses of two trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the RR of normal visual acuity (defined as 20/20 Snellen fraction or equivalent) in the intravenous corticosteroids group compared with the placebo group was 1.05 (95% CI 0.88 to 1.26; participants = 346) at six months. The RR of contrast sensitivity in the normal range for the same comparison was 1.11 (95% CI 0.92 to 1.33; participants = 346) at six months follow-up. The RR of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.21; 346 participants) at six months; and 1.01 (95% CI 0.86 to 1.19; participants = 316) at one year. Four trials reported adverse events primarily related to gastrointestinal symptoms and sleep disturbance; one trial reported minor adverse event of acne.
AUTHORS' CONCLUSIONS
There is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity six months after initiation with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review.
Topics: Acute Disease; Administration, Oral; Anti-Inflammatory Agents; Contrast Sensitivity; Dexamethasone; Female; Glucocorticoids; Humans; Injections, Intravenous; Male; Methylprednisolone; Optic Neuritis; Prednisone; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 26273799
DOI: 10.1002/14651858.CD001430.pub4 -
Journal of Veterinary Internal Medicine May 2020Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects.
BACKGROUND
Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects.
HYPOTHESIS/OBJECTIVES
Determine the effects of clopidogrel and prednisone on platelet function.
ANIMALS
Twenty-four healthy dogs.
METHODS
Double-blinded, placebo-controlled randomized trial. Platelet function was evaluated using a platelet function analyzer and impedance aggregometry (days 0, 14, and 28) for dogs treated with placebo, clopidogrel (2-3 mg/kg/d), prednisone (2 mg/kg/d), or prednisone with clopidogrel PO for 28 days. Results were categorized as nonresponder versus responder (platelet function analyzer), and inadequate, ideal, or excessive response (aggregometry). Results were compared using mixed model, split-plot repeated measures analysis of variance and generalized estimating equation proportional odds models. P < .05 was considered significant.
RESULTS
Closure times differed by treatment (F [3, 20] = 10.5; P < .001), time (F [2, 40] = 14.3; P < .001), and treatment-by-time (F [6, 40] = 3.4; P = .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P < .001), time (F [2, 40] = 35.4; P < .001), and treatment-by-time (F [6, 40] = 13.5; P < .001). Based on closure times, 5/6 dogs each in the clopidogrel and prednisone/clopidogrel groups were responders. All dogs in the prednisone/clopidogrel group were overcontrolled based on AUC (days 14 and 28), whereas 5/6 (day 14) and 2/6 (day 28) dogs treated with clopidogrel were overcontrolled. Compared to clopidogrel, dogs receiving prednisone/clopidogrel were 11 times (P = .03) more likely to have an excessive response.
CONCLUSIONS AND CLINICAL IMPORTANCE
Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs.
Topics: Animals; Blood Platelets; Clopidogrel; Dogs; Drug Interactions; Female; Glucocorticoids; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prednisone
PubMed: 32246893
DOI: 10.1111/jvim.15759