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Expert Review of Clinical Immunology Mar 2021Polymyalgia rheumatica (PMR) is a common inflammatory disease found in people older than 50 years of Northern European descent. It is characterized by pain and... (Review)
Review
INTRODUCTION
Polymyalgia rheumatica (PMR) is a common inflammatory disease found in people older than 50 years of Northern European descent. It is characterized by pain and stiffness in the shoulders, arms, hips, and neck. Relapses are common in patients with PMR.
AREAS COVERED
This review describes when and how relapses occur in patients with PMR. Potential predisposing factors associated with relapses and management are also discussed. An extensive literature search on the PubMed database was conducted for publications on 'polymyalgia rheumatica' AND 'relapses' AND 'risk factors'.
EXPERT OPINION
Relapses are common in PMR being observed in approximately half of the patients. They often occur when the dose of prednisone is below 5-7.5 mg/day. The speed of glucocorticoid tapering is considered to be the main factor influencing the development of relapses in isolated PMRs. In addition, a genetic component may favor the presence of relapses in isolated PMRs. HLA-DRB1*0401 alleles were associated with an increased risk of relapse. An implication of the IL-6 promoter -174 G/C polymorphism and the GG241 ICAM-1 genotype was also reported. With regard to serological biomarkers, elevated levels of angiopoietin-2 were associated with an unfavorable course of PMR. Methotrexate and anti-IL6 receptor antibody tocilizumab may be required in PMR patients with multiple relapses.
Topics: Humans; Polymyalgia Rheumatica; Prednisone; Recurrence; Risk Factors
PubMed: 33570454
DOI: 10.1080/1744666X.2021.1890032 -
The Israel Medical Association Journal... Dec 2022Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials,... (Review)
Review
BACKGROUND
Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.
OBJECTIVES
To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.
METHODS
We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.
RESULTS
The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.
CONCLUSIONS
All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.
Topics: Humans; Anti-Asthmatic Agents; Prednisone; Cohort Studies; Asthma; Biological Products
PubMed: 36573775
DOI: No ID Found -
Revista Da Associacao Medica Brasileira... Apr 2022The aim of this study was to analyze the occurrence and risk factors associated with infections during pregnancy in patients with systemic lupus erythematosus.
OBJECTIVE
The aim of this study was to analyze the occurrence and risk factors associated with infections during pregnancy in patients with systemic lupus erythematosus.
METHODS
This is a retrospective cohort study using the data of pregnant women who were followed up between 2011 and 2018 at a university hospital.
RESULTS
The data of 221 pregnant women with systemic lupus erythematosus were analyzed. The incidence of infections was 22.6% (50/221), with the urinary tract being the most frequent site of infection (32/221, 14.5%) followed by the respiratory tract (15/221, 6.8%). The bivariate analysis showed that active disease, hematological systemic lupus erythematosus, reduced complement, and use of prednisone ≥5 and ≥10 mg increased the chance of infection during early pregnancy (p=0.05, p=0.04, p=0.003, p=0.008, and p=0.02, respectively), while disease activity and anti-DNA positivity increased it at the end of pregnancy (p=0.03 and p=0.04, respectively). Prednisone at a dose ≥5 mg increased the chance of infection in the beginning (p=0.01) and at the end of pregnancy (p=0.008). Multivariate analysis showed that increasing the dose of prednisone from 5 to 10 mg tripled the chance of developing infections in pregnant women with lupus (p=0.02).
CONCLUSION
The study showed an increased chance of infections in pregnant women with systemic lupus erythematosus and it was associated with the use of prednisone.
Topics: Female; Humans; Lupus Erythematosus, Systemic; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Retrospective Studies; Risk Factors
PubMed: 35649080
DOI: 10.1590/1806-9282.20220074 -
Lupus Jun 2022We aimed to study the daily dose of glucocorticoids in the first month associated with damage after 5 years of systemic lupus erythematosus (SLE) diagnosis; and to...
OBJECTIVES
We aimed to study the daily dose of glucocorticoids in the first month associated with damage after 5 years of systemic lupus erythematosus (SLE) diagnosis; and to assess the daily dose of prednisone during the first year, over which damage after 5 years could be predicted.
METHODOLOGY
A retrospective cohort study of SLE patients from the diagnosis and up to 5 years of follow-up was performed. Cumulative prednisone doses in the first month (T1m), at 1 year (T12m), and at 5 years (T5y) were calculated. Damage was estimated using the SLICC index and activity by the SLEDAI-2K. Damage at T5y was categorized as "present" or "absent". To determine the cutoff point of prednisone dose for the first month and for the first year of treatment, related to damage at 5 years, a ROC curve was done. A logistic regression was performed to control damage at 5 years by the activity levels, anti-DNA titers, and the corticosteroid burden between 1 and 5 years.
RESULTS
Forty-eight patients were included with a mean age of 42.4 (12.6) years; 46 (95.8%) were female. The cumulative dose in T1m associated with greater sensitivity and specificity in the ROC curve (1.54; AUC 0.793; 95% CI: 0.66-0.92) to predict glucocorticoid-related damage at 5 years of follow-up was 980mg, which leads to a daily dose for the first month of 32.6 mg/day. The daily dose during the first year associated with damage at 5 years, allowed to calculate an optimal cutoff point of 7.38 mg/day, with a sensitivity of 92.9% (AUC 0.695, 95% CI: 0.52-0.86) to predict damage at 5 years. In the logistic regression, this estimate was maintained, controlling for SLEDAI-2K and for positivity or not of anti-DNA antibodies and for the cumulative dose of prednisone between T5y and T12m.
CONCLUSION
This pilot study allows to estimate a threshold dose of 32.6 mg/day during the first month and 7.38 mg/day during the first year, over which the risk of permanent damage is high at 5 years, regardless of the activity levels and the glucocorticoid doses considered between the first and the fifth year of follow-up.
Topics: Adult; Antibodies, Antinuclear; Female; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Male; Pilot Projects; Prednisone; Retrospective Studies; Severity of Illness Index
PubMed: 35354060
DOI: 10.1177/09612033221093485 -
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 -
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 -
Postgraduate Medicine Nov 2022Lane-Hamilton syndrome (LHS) presents a medical emergency, with 14% mortality due to Idiopathic Pulmonary Hemosiderosis (IPH) in acute phase. Despite the clinical... (Review)
Review
Lane-Hamilton syndrome (LHS) presents a medical emergency, with 14% mortality due to Idiopathic Pulmonary Hemosiderosis (IPH) in acute phase. Despite the clinical severity of this entity, there has been no published review in the international literature, resulting in lack of awareness and delayed diagnosis.A rigorous search of international databases yielded a total of 80 LHS cases from January 1971 to August 2020. We analyzed 44 children (8.56 ± 4.72 years, 21 boys) and 36 adults (33.61 ± 13.41 years, 12 men) to present the clinical manifestations, radiological and immunological pattern, therapeutic approaches and outcome of LHS. We also elaborated on clinical and laboratory findings' associations to propose diagnostic indexes and clarified differences based on age distribution.Celiac disease (CD) and IPH diagnosis was made concurrently in 46 patients, whereas in 21 patients, the diagnosis of LHS was delayed for 2.5y (3 months-11 years). Hemoptysis ( = 56, 70%), dyspnea ( = 47, 58.8%), anemia ( = 72, 90%), and iron deficiency ( = 54, 67.5%) were most commonly observed. Medical history revealed recurrent episodes of hemoptysis ( = 38) and persistent iron deficiency anemia ( = 25) in need of multiple blood transfusions or iron supplementation. Patchy infiltrate opacities to consolidation predominated in children, whereas bilateral diffuse ground-glass opacities in adults. Duodenal biopsy was performed in 66 cases (diagnostic 87.8%), BAL in 51 (diagnostic 74.5%), and surgical lung biopsy in 20. Anti-tTG titer was positive in all 24 (54.6%) children and 19 (52.8%) adults that documented this assay. Prednisone or methylprednisolone pulse therapy and GFD were initiated in the acute phase, whereas chronic therapy included GFD, along with long-term prednisone in refractory cases. Three cases with severe respiratory failure or hemodynamic instability were intubated and a further three succumbed.A thorough understanding of LHS may reveal further diagnostic indexes and a consensus on therapy guidelines. Screening for CD is essential in all IPH cases for timely recognition and favorable outcome.
Topics: Child; Male; Adult; Humans; Celiac Disease; Hemoptysis; Prednisone; Hemosiderosis; Lung Diseases; Anemia; Hemosiderosis, Pulmonary
PubMed: 35912848
DOI: 10.1080/00325481.2022.2109121 -
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 -
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