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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 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 -
Biochemical Pharmacology Jul 2019Glucocorticoids (GCs) constitute a first line treatment for many autoimmune and inflammatory diseases. Due to their potent anti-inflammatory and immunosuppressive... (Review)
Review
Glucocorticoids (GCs) constitute a first line treatment for many autoimmune and inflammatory diseases. Due to their potent anti-inflammatory and immunosuppressive actions, GCs are added frequently to disease modifying antirheumatic drugs (DMARDs) in various arthritic diseases, such as rheumatoid arthritis. However, their prolonged administration or administration at high doses is associated with adverse effects that may be (quality of) life-threatening, including osteoporosis, metabolic, gastrointestinal and cardiovascular side effects. In this review, we summarize the clinical and pharmacological effects of GCs in different arthritic diseases, while documenting the current research efforts towards the identification of novel and more efficient GCs with reduced side effects.
Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Humans; Prednisone
PubMed: 30978323
DOI: 10.1016/j.bcp.2019.04.009 -
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 -
Lupus Jul 2021Systemic lupus erythematosus (SLE) management objectives include preventing disease flares while minimizing glucocorticoid exposure. Pooled data from the phase 3 TULIP-1... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Systemic lupus erythematosus (SLE) management objectives include preventing disease flares while minimizing glucocorticoid exposure. Pooled data from the phase 3 TULIP-1 and TULIP-2 trials in patients with moderate to severe SLE were analyzed to determine anifrolumab's effect on flares, including those arising with glucocorticoid taper.
METHODS
TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks for 48 weeks). For patients receiving baseline glucocorticoid ≥10 mg/day, attempted taper to ≤7.5 mg/day prednisone or equivalent from Weeks 8-40 was required and defined as sustained reduction when maintained through Week 52. Flares were defined as ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B scores versus the previous visit. Flare assessments were compared for patients receiving anifrolumab versus placebo.
RESULTS
Compared with placebo (n = 366), anifrolumab (n = 360) was associated with lower annualized flare rates (rate ratio 0.75, 95% confidence interval [CI] 0.60-0.95), prolonged time to first flare (hazard ratio 0.70, 95% CI 0.55-0.89), and fewer patients with ≥1 flare (difference -9.3%, 95% CI -16.3 to -2.3), as well as flares in organ domains commonly active at baseline (musculoskeletal, mucocutaneous). Fewer BILAG-based Composite Lupus Assessment responders had ≥1 flare with anifrolumab (21.1%, 36/171) versus placebo (30.4%, 34/112). Of patients who achieved sustained glucocorticoid reductions from ≥10 mg/day at baseline, more remained flare free with anifrolumab (40.0%, 76/190) versus placebo (17.3%, 32/185).
CONCLUSIONS
Analyses of pooled TULIP-1 and TULIP-2 data support that anifrolumab reduces flares while permitting glucocorticoid taper in patients with SLE.TULIP-1 NCT02446912 (clinicaltrials.gov/ct2/show/NCT02446912);TULIP-2 NCT02446899 (clinicaltrials.gov/ct2/show/NCT02446899).
Topics: Antibodies, Monoclonal, Humanized; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Prednisone
PubMed: 33977796
DOI: 10.1177/09612033211014267 -
Pediatric Nephrology (Berlin, Germany) Feb 2022The therapeutic efficacy of B cell-depleting anti-CD20 treatment in both pediatric and adult steroid-sensitive nephrotic syndromes (SSNS) suggests that B cells play a...
BACKGROUND
The therapeutic efficacy of B cell-depleting anti-CD20 treatment in both pediatric and adult steroid-sensitive nephrotic syndromes (SSNS) suggests that B cells play a pathogenic role in the disease. In adults with minimal change disease (MCD), only circulating plasmablasts are increased during the active phase of the disease, among B cell subsets. These cells have not been studied yet in children with SSNS.
METHODS
We retrospectively quantified by flow cytometry analysis circulating plasmablasts in 107 pediatric patients with SSNS (51 at disease onset, 27 during relapse, and 29 in remission). Data were compared with an equal number of age- and sex-matched healthy donors (HD).
RESULTS
Circulating plasmablast levels, expressed as percentage of total CD19 B cells or as percentage of total lymphocytes, were normal in all SSNS subgroups, compared to HD. Patients in remission had significantly fewer circulating plasmablasts compared to patients at disease onset. No significant correlation was observed between plasmablast levels and proteinuria or serum proteins, at onset. Treatment with prednisone and mycophenolate mofetil significantly reduced circulating levels of plasmablasts, unlike treatment with prednisone and calcineurin inhibitors.
CONCLUSIONS
The B cell phenotype of children with SSNS differs from that of adults with MCD. This may justify different therapeutic approaches.
Topics: Child; Female; Humans; Male; Nephrosis, Lipoid; Nephrotic Syndrome; Plasma Cells; Prednisone; Retrospective Studies
PubMed: 34661744
DOI: 10.1007/s00467-021-05273-8 -
Journal of Cardiac Failure Dec 2021Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack...
BACKGROUND
Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment.
METHODS AND RESULTS
This retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200-2760 mg] vs 2710 mg [IQR, 1200-5080 mg]; P = .06). On F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7-9.0, P = .002) and 2.9 (IQR 0-5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated.
CONCLUSIONS
Mycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects.
Topics: Adult; Heart Failure; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisone; Retrospective Studies; Sarcoidosis
PubMed: 34166800
DOI: 10.1016/j.cardfail.2021.06.010 -
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 -
Autoimmunity Reviews Oct 2015To compare the efficacy and safety of high vs. low-moderate oral doses of prednisone to treat patients with highly active lupus at diagnosis. (Comparative Study)
Comparative Study Review
OBJECTIVE
To compare the efficacy and safety of high vs. low-moderate oral doses of prednisone to treat patients with highly active lupus at diagnosis.
PATIENTS AND METHODS
Patients from the Lupus-Cruces cohort with an SLEDAI score ≥6 at diagnosis and treated with regimes containing low-medium prednisone doses (≤30 mg/day) were identified (group M). They were matched by sex and SLEDAI score with historical patients treated with high doses (>30 mg/day) at diagnosis (group H). Patients with proliferative nephritis were excluded. The difference in SLEDAI scores between baseline (SLEDAI-0) and year one (SLEDAI-1) was the efficacy variable. Damage at 5 years was calculated using the SLICC damage index (SDI) and regarded as the safety variable. Glucocorticoid related damage was considered in the presence of cataracts, osteonecrosis, osteoporotic fractures and/or diabetes mellitus.
RESULTS
30 patients were included in each group. Patients in group H received 5-fold higher doses of prednisone, less hydroxychloroquine and less methyl-prednisolone pulses. SLEDAI improvement was similar in both groups. Patients in group H were more likely to accrue new damage (adjusted HR 3.85 (95% CI 1.03-14.2)). No patients in group M suffered glucocorticoid-related damage, vs. 5 patients in group H (p=0.02). The average daily prednisone dose during the first year predicted accrual of new damage (adjusted HR 1.03, 95% CI 1.0-1.07, p=0.056) and accrual of glucocorticoid-related damage (adjusted HR 1.06, 95% CI 1.01-1.13, p=0.03). Likewise, average doses of prednisone >7.5mg/day were an independent predictor of new damage (adjusted HR 4.8, 95% CI 1.2-19.1).
CONCLUSION
Prednisone doses ≤30 mg/day are similarly effective and safer than higher doses for treating active lupus.
Topics: Glucocorticoids; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Methylprednisolone; Prednisone
PubMed: 26044819
DOI: 10.1016/j.autrev.2015.05.011