Prednisone Group Research Articles

FC057: Incidence of Infections in the Avacopan Group Versus Prednisone Group in Anca-Associated Vasculitis, Results from the Phase 3 Advocate Study

Abstract BACKGROUND AND AIMS Standard therapy for ANCA-associated vasculitis (AAV) includes glucocorticoids (GC), which are associated with increased infections. Avacopan is an orally administered selective inhibitor of the C5a receptor recently approved for treatment of AAV. The phase 3 ADVOCATE study tested daily avacopan as a substitute for a standard, scheduled, daily oral GC tapered regimen (all with standard background therapy), resulting in a 63% mean reduction in overall GC load for the avacopan group. At week 26, the avacopan group achieved a comparable remission rate to prednisone (72.3% versus 70.1%) and superior sustained remission at Week 52 (65.7% versus 54.9%; one-sided P = 0.0066) (1). The present analysis compared infections in avacopan and prednisone groups in the ADVOCATE trial. METHOD ADVOCATE, a phase 3, randomized, double-blind, controlled trial in 330 patients, evaluated the efficacy and safety of avacopan. AAV patients (new onset or relapsing disease) were randomized to receive avacopan 30 mg twice daily, or a standard 20-week oral prednisone taper, plus matching placebos. Both groups had background therapy of either cyclophosphamide (followed by azathioprine) or rituximab, and additional GC exposure from premedication for rituximab, from taper of pre-randomization GC, and as required per investigator judgment. Patients were on blinded study drug for 52 weeks. Infections occurring from first dose of blinded study drug through day 56 after last dose were analyzed. RESULTS Total mean GC use during the first 26 weeks of the study was 1073 mg with avacopan and 3193 mg with prednisone groups, and in the last 26 weeks, 296 and 489 mg, respectively. Infections were higher in the prednisone group than with avacopan: 291 events (prednisone) versus 233 (avacopan), with a 75.6% incidence (124/164) with prednisone versus 68.1% (113/166) with avacopan (Table 1). During the prednisone taper period (first 20 weeks), infection incidence was 54.9% in prednisone group versus 49.4% for avacopan, and after the first 20 weeks 52.4% in prednisone group versus 44.0% avacopan. Fewer patients in the avacopan group experienced serious AEs of infection (13.3%/25 events) versus prednisone group (15.2%/31 events); also serious opportunistic infections (3.6% versus 6.7%), life-threatening AEs of infection (0.6% versus 1.2%), and infections resulting in death (0.6% versus 1.2%) were fewer with avacopan (Table 1). No Neisseria meningitidis infections occurred in any patient in the trial. CONCLUSION In the ADVOCATE trial, the mean dose of GCs from all sources was 63% lower in the avacopan group than the prednisone group (1349 versus 3655 total mg, respectively). The avacopan group had a numerically lower incidence of infections, including serious, life-threatening, fatal and serious opportunistic infections compared with the prednisone group.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5mg/kg/day) and a control group, which was administered saline solution for 30days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1β, IL-6, TNF-α and TRAP. Despite after 7days, there was no differences between groups, a significant increase in the root pulp necrosis (p=.001), micro-abscesses (p=.026) and the size of the apical lesion on the 14th day of treatment with prednisone (p=.008). On the same day, there was also an increase in the number of polymorphonuclear cells (p=.042) and cells immunostained for IL-1β (p=.006), IL-6 (p<.001) and TRAP (p=.002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28days (p=.025) and TNF-α ± increases in the prednisone group on the 7th day (p=.041). The prednisone group also showed a decrease in collagen after 14 (both type I [p=.041] and type III [p=.046]) and 28 type III (p=.002) days after the coronary opening. The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy

Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017. Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. ClinicalTrials.gov Identifier: NCT01603407.

Hemostatic mechanism of the effect of Jianpi Yiqi Shexue decoction on vascular factors in immune thrombocytopenia model mice

To explore the hemostatic mechanism of Jianpi Yiqi Shexue decoction (JYSD) by regulating vascular factors in an immune thrombocytopenia (ITP) mouse model. An ITP mouse model was established by the passive-immune modeling method, and interventional drugs used were prednisone tablets and JYSD. The platelet count; vascular activity–related factors vWF, VCAM-1, and TM; and VEGF and bFGF were used as observational indicators. On the 8th day of administration, compared with the model group, platelet counts in the prednisone and JYSD groups increased (both P < .001). Compared with the control group, the levels of vWF, VCAM-1, and TM in the other groups were lower (all P < .05). The VCAM-1 level in the JYSD group was higher than that in the prednisone group ( P = .012), but without significant difference compared with the model group ( P = .051). The TM level in the JYSD group was the lowest ( vs. the model group, P = .047; vs. the prednisone group, P = .006). Compared with the control group, the IOD values of VEGF and bFGF in the other three groups were lower (all P < .01). The IOD values of VEGF in the prednisone and JYSD groups were both higher than those in the model group ( P = .002 and P < .001, respectively). The IOD values of bFGF among the model, prednisone, and JYSD groups were not statistically significant ( P > .05). A vascular factor disorder is involved in the pathogenesis of ITP. JYSD can increase the platelet count, upregulate VEGF expression, and reduce the TM level. JYSD has the same effect as prednisone tablets in regulating platelet, vWF, VEGF, and bFGF, with a stronger effect in normalizing VCAM-1 and TM levels. The hemostatic mechanism of JYSD is closely related to the effective balance of vascular factors.

Prednisone Ameliorates Atrial Inflammation and Fibrosis in Atrial Tachypacing Dogs.

Atrial inflammation and fibrosis have long been considered culprits in the development of atrial fibrillation (AF). Prior clinical studies showed that corticosteroid therapy is beneficial in patients with AF. Here we sought to determine whether prednisone treatment prevents atrial tachypacing (ATP) induced atrial fibrosis.Dogs were randomized into the sham, ATP, ATP + low-dose prednisone (ALP), and ATP + high-dose prednisone (AHP) groups. After 6 days of recovery from surgery, dogs were subjected to ATP at 400 beats per minute for 4 weeks while being treated with prednisone (15 or 40 mg/day) or a placebo. Pacemakers were not activated in the sham group.Compared with the ATP group, the expression of collagen I, collagen III, α-smooth muscle actin, transforming growth factor-β1 and connective tissue growth factor were significantly reduced in the ALP and AHP groups. Fluorescence assays showed that reactive oxygen species formation in the right atrium was suppressed in the ALP and AHP groups compared with the ATP group. The protein level of NADPH oxidase 2 was reduced in the ALP and AHP groups' versus ATP group, while NOX4 and NOX5 were unchanged. ATP-induced downregulation of BH4 and eNOS uncoupling in the atria was partially restored in the prednisone-treated groups.Our study demonstrated that atrial fibrosis induced by ATP were suppressed by prednisone. Low-dose prednisone was also effective in suppressing the development of atrial fibrosis.

A Randomized Open-Labeled Trial of Methotrexate as a Steroid-Sparing Agent for Patients With Generalized Myasthenia Gravis.

Background and PurposeTwo 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.MethodsWe 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.ResultsForty 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, p = 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 (p = 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.ConclusionsThis 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.

Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: Multicentre real-world observational study.

Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.

POS-444 EFFECT OF AVACOPAN, A SELECTIVE C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and renal disease have a poor prognosis. The effect of avacopan, an oral C5a receptor inhibitor, on renal function is described. The ADVOCATE Phase 3 trial randomized patients to receive avacopan or prednisone taper on a background of either cyclophosphamide (followed by azathioprine) or rituximab. Primary endpoints were remission at Week 26 and sustained remission at Week 52. Secondary objectives included evaluation of kidney function. At Week 52, the difference in eGFR recovery in patients with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline between avacopan and prednisone treatment groups was 5.5 mL/min/1.73 m2(95% CI [1.4, 9.6], p<0.01) (Figure 1A ). Improvement in eGFR with avacopan was most prominent in patients with eGFR <30 mL/min/1.73 m2at baseline, when by week 52, the least squares mean (LSM) increase in eGFR was 13.7 (avacopan group) vs. 8.2 mL/min/1.73 m2(prednisone group) (p<0.01) (Figure 1B) . Among patients with CKD Stage 4 at baseline: in the avacopan group (n=52), 26 (50%) improved 1 stage and 3 (5.8%) improved 2 stages; in the prednisone group (n=48), 21 (44%) improved 1 stage and 1 (2.1%) improved 2 stages (p=0.32). Avacopan was also associated with more rapid reduction in proteinuria and hematuria. Urinary albumin:creatinine ratio improved 40% within the first 4 weeks of treatment with avacopan vs. no change in the prednisone group (difference -40, 95% CI [-53, -22]). Figure 1. Change in Renal Function Through Week 52 In ADVOCATE, patients with ANCA-associated vasculitis in the avacopan group had greater recovery of kidney function compared to patients in the prednisone group, especially among patients with CKD Stage 4 and those with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline.

Avacopan, a selective C5a receptor antagonist, for anti-neutrophil cytoplasmic antibody-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, has been approved for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan and the USA. In ADVOCATE Phase III clinical trial, patients with active MPA or GPA received either 30 mg avacopan twice daily or prednisone on a tapering schedule in combination with rituximab or cyclophosphamide (followed by azathioprine). The trial met its two primary endpoints: avacopan showed non-inferiority to prednisone for achieving remission at Week 26 (avacopan, 72.3%; prednisone, 70.1%; p < .001 for non-inferiority and p = .24 for superiority) and superiority for maintaining remission at Week 52 (65.7% for avacopan, 54.9% prednisone, p < .001 for non-inferiority and p = .007 for superiority). Of several key secondary endpoints tested, the glucocorticoid toxicity index (GTI)-cumulative worsening score and GTI-aggregate improvement score were significantly lower in the avacopan group than in the prednisone group at both Weeks 26 and 52. Serious adverse events related and unrelated to the worsening vasculitis were reported at 10.2% and 37.3% in the avacopan group and at 14.0% and 39.0% in the prednisone group, respectively. Avacopan has set the stage for the semi-glucocorticoid-free or glucocorticoid-free treatment of MPA and GPA.

Prednisone plus IVIg compared with prednisone or IVIg for immune thrombocytopenia in pregnancy: a national retrospective cohort study.

Background:The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP).Methods:Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone.Results:Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8–195 days), whereas that in the combination group was 14 days (range, 6–85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone.Conclusion:These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

Avacopan: An Oral Complement 5a Inhibitor for ANCA-associated Vasculitis

The oral complement 5a receptor antagonist, avacopan, was recently studied in phase II and III clinical trials in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article summarizes the study findings and considers the implications for future care of patients with AAV. Avacopan was proven to be safe and noninferior to glucocorticoids for AAV in a study where patients with severe newly diagnosed or relapsing AAV were initially treated with either rituximab or cyclophosphamide. Greater improvement in the glomerular filtration rate, reduced numbers of relapses and better health-related quality of life were observed in the avacopan group compared with the prednisone group. Patients in the avacopan group also had fewer glucocorticoid-associated adverse events and, despite complement inhibition, there were no cases of Neisseria meningitidis infection reported in either group. Future studies should address the long-term safety of avacopan and whether it can completely replace glucocorticoids in AAV-induction protocols and for the management of minor disease relapses.

Does transitory steroid-induced central hypothyroidism in children treated for haematological malignancies warrant clinical intervention?

Steroid-induced central hypothyroidism (CH) is a frequent but under-diagnosed hormonal disturbance in children treated for acute lymphoblastic leukaemia (ALL) and lymphoma. To determine the occurrence, frequency of symptoms, replacement therapy administration, and association of CH with glucocorticoid therapy in children treated for haematological malignancies. A prospective clinical survey was conducted on 21 patients (61.9% male, mean age 9.1 years) treated in the Children's Hospital Zagreb during 2019, of whom 12 were treated for for ALL and 6 for Hodgkin lymphoma (HL), based on clinical (signs and symptoms) and laboratory data (hormonal status). Overt CH was verified in 15 (71.4%) and mild CH in 3 patients (14.2%). The most common symptoms and signs were fatigue, apathy, and electrolyte imbalance, observed in 50% of CH cases. Hormonal substitutional therapy was initiated in 44.4% of affected patients, during a mean of 2.08 months, with significant clinical improvement. Overt CH was more prevalent in patients with ALL than in those with HL (p = 0.025). Among children with ALL there was no difference in CH occurrence between the prednisone and dexamethasone groups; however, dexamethasone-induced CH was more frequently symptomatic (p = 0.03). The prednisone dosage played no role in CH incidence in patients with HL. Further studies are needed to determine the real incidence of thyroid dysfunction during intensive chemotherapy treatment in children with ALL and lymphoma. Recommendations for optimal hormonal replacement therapy and a follow-up plan for paediatric oncology patients with CH are also urgently required.

Treatment response, risk of relapse and clinical characteristics of Taiwanese patients with neuromyelitis optica spectrum disorder

The long-term disease course and efficacy of maintenance therapies have rarely been investigated in Asian patients with neuromyelitis optica spectrum disorder (NMOSD). Medical records of patients fulfilling the 2015 International Consensus Diagnostic Criteria for NMOSD at three medical centers in Taiwan were systematically analyzed. Linear regression analysis was performed to investigate factors related to annualized relapse rate (ARR); survival analysis was used to estimate the relapse-free intervals among therapies. A total of 557 relapses affecting 648 regions (202 optic neuritis, 352 acute myelitis, and 94 brain syndromes) in 204 patients were analyzed during a follow-up period of 69.5 months (range, 1-420). Up to 36.1% of myelitis-onset patients and 24.0% of optic neuritis-onset patients exhibited a limited form disease, defined as having one or more relapses confined to the same region. The median ARR was significantly lower in patients with limited form disease than those with relapses involving multiple regions (0.30 vs. 0.47, respectively). An older age at disease onset was associated with a lower ARR (p=0.023). Kaplan-Meier analysis showed that the estimated time (months) to next relapse was longest in rituximab-treatment group (58.0±13.2), followed by immunosuppressant (48.5±4.8) or prednisone (29.6±4.6) groups, and shortest in those without maintenance therapy (27.6±4.2) (p=8.1×10-7). Limited form disease and older age at disease onset are associated with a lower relapse rate in NMOSD. Compared to no maintenance therapy, rituximab and immunosuppressant significantly reduce the relapse risks.

Estimates of minimal clinically important improvments vary with the responsiveness of the sample

ObjectiveMinimal clinically important improvements (MCII) are known to vary with the baseline level in the sample. We examined if MCIIs are also larger in samples with higher responsiveness. Study design and settingIn a prospective longitudinal study of patients with active rheumatoid arthritis, we assessed arthritis activity before and after new treatments. We estimated anchor-based MCIIs for three outcomes (pain severity, physical functioning by the Health Assessment Questionnaire, and Simplified Disease Activity Index, a composite measure) using receiver operating characteristic curves. We compared MCIIs among patients treated with three interventions of different impact (dose escalation, new disease-modifying medication, or prednisone). Separately, we used simulations to estimate MCIIs in five groups of responsiveness. ResultsAmong 250 patients, standardized response means (SRMs) increased across the dose escalation, disease-modifying treatment, and prednisone treatment groups (-0.74, -1.00, and -1.53, respectively). MCIIs were also highest in the prednisone group. For example, corresponding MCIIs were -5.5, -8.9, and -13.8 for the composite measure. In the simulations, MCIIs (range -4.6 to -11.9) varied directly with SRMs (range -0.40 to -1.33). Results were similar for pain and the Health Assessment Questionnaire. ConclusionThe MCII is not an intrinsic measurement property but varies directly with sample responsiveness.

Adverse Side Effects Associated with Corticosteroid Therapy: A Study in 39 Patients with Generalized Myasthenia Gravis.

BackgroundThe tolerability of high-dose oral corticosteroids in patients with generalized myasthenia gravis (gMG) has not been systematically assessed. We evaluated adverse side effects (ASEs) of corticosteroid treatment in patients with gMG.Material/MethodsRetrospective analysis was conducted of ASEs reported as being related to corticosteroid treatment in 39 patients with gMG who were treated with oral corticosteroids for ≥1 year.ResultsMedian (interquartile range [IQR]) age was 60 (21) years, 53.8% of patients were women, and 66.7% were aged ≤65 years. Median (IQR) prednisone treatment duration was 14 (2) months; median (IQR) daily dose was 40 (15) mg. The median number of ASEs reported as corticosteroid-related was 2/patient (IQR, 1). Pre-diabetes and weight gain were most common (each 43.6% of patients). Bruising, insomnia, and osteoporosis were more prevalent in patients aged >65 years, while irritability, osteopenia, and pre-diabetes were more common in patients aged ≤65 years, although differences were not statistically significant. Irritability and weight gain were more prevalent in women (P=0.010 for irritability); osteoporosis and pre-diabetes more common in men (P=0.015 for osteoporosis). ASEs were generally more common in the high-dose prednisone group (>30 mg/day), but were only statistically significant for irritability (P=0.001).ConclusionsCorticosteroid-related ASEs were common in patients with gMG. Some of these ASEs can have serious medical consequences, and certain ASEs appeared to be associated with specific patient characteristics. Demographics and comorbidities of patients with gMG must be carefully considered before corticosteroid initiation. Potential ASEs, such as unanticipated osteoporosis in men, require extra vigilance.

Corticosteroids in tuberculous pericarditis whit severe pericardial effusion to avoid constriction: a retrospective study in HIV-negative population

Abstract The role of corticosteroids in the treatment of tuberculous aetiology pericarditis without human immunodeficiency virus (HIV) is not well defined. Is unclear if associating corticoids to regular antibiotic therapy for tuberculosis, can prevent the progression of a severe pericardial effusion to constrictive pericarditis. Despite that, in countries where tuberculosis is an endemic disease and mostly it's not related to HIV, the use of corticosteroids is a common practice, as a part of a strategy to avoid progression of a severe pericardial effusion to a constrictive pericarditis. Our aim is to describe the clinical course of the patients with severe pericardial effusion of tuberculous aetiology and no echocardiographic sings of constriction, distinguishing those who used corticosteroids from those who didn't. We conducted a retrospective study, analyzing the clinical files of 40 patients treated in one hospital in a 5 years period (2016–2021). All of these patients were diagnosed whit severe pericardial effusion of tuberculous aetiology and no signs of constrictive pericarditis, they all finished their specific antibiotic treatment protocol according national guidelines and had at least 2 years of clinical follow from the time of the diagnosis. We found that the mean age was 54 years, 55% were men and 45% women. The mean follow up was 2.6 years. In all patients pericardial drainage was preformed, 60.5% using closed pericardiocentesis and 39.5% using open surgical techniques. 22 patients (55%) received prednisone that was initiated whit a dose of 1mg/kg daily that was reduced weekly in order to complete a 2 month cycle. The other 18 patients (45%) didn't received corticosteroids. In the prednisone group, 3 patients develop constrictive pericarditis during the time of follow up (13.6% of the prednisone group) while 7 patients of the non-corticosteroids group (38.8%) develop constrictive pericarditis. These retrospective study shows that there is a potential reduction in the progression to constrictive pericarditis whit the use of prednisone in HIV negative patients whit severe pericardial effusion of tuberculous aetiology, we need to perform prospective, controlled, blind and multicenter studies, designed to evidence the real effect of these strategy. Funding Acknowledgement Type of funding sources: None. Cases of contriction in both groups

Clinical evaluation of efficacy of leflunomide combined with low-dose prednisone for treatment of myasthenia gravis.

This study evaluated the clinical efficacy of leflunomide combined with low-dose prednisone (0.25mg/kg/day) for treatment of myasthenia gravis (MG). We enrolled 32 MG patients treated with leflunomide combined with low-dose prednisone. In the control group, 14 patients were treated with low-dose prednisone. Improvement in MG composite (MGC) score of ≥ 3 points from enrollment to 12-week follow-up indicated that the treatment was effective. In the leflunomide combined low-dose prednisone group, the median of MGC score at the time of enrollment was 8.5 points. After 12weeks, the MGC score dropped to four points. There was statistically significant difference in MGC score before and after treatment (p < 0.001). In the low-dose prednisone group also followed up for 12weeks, the median of MGC score of the patients decreased from 7 to 4 points, and the change was not statistically significant (p = 0.05). In the leflunomide combined low-dose prednisone group, the improvement of clinical symptoms occurred mainly in the first 4weeks and the last 4weeks. Relatively, the decline of the score was mostly seen during the first 8weeks in the low-dose prednisone group. In leflunomide combined with low-dose prednisone group, the effective rate of generalized MG(gMG) was significantly higher than ocular MG(oMG) (χ2 test, p = 0.036). However, there is no significant difference in the effective rate between AChR-Ab-positive and -negative groups (Fisher's Exact Test, p = 0.625). No serious side effects were observed in any of the subjects. Leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of patients with MG. It may be a promising treatment for gMG.

Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID‐19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo‐controlled trial that compared a 7‐day treatment course of 50‐mg prednisone to placebo in patients hospitalized with community‐acquired pneumonia. We compared levels of C‐reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community‐acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.

Imperatae rhizoma-Hedyotis diffusa Willd. herbal pair alleviates nephrotic syndrome by integrating anti-inflammatory and hypolipidaemic effects

BackgroundNephrotic syndrome (NS) is a common nephropathy with a complex and diverse aetiology. Both Imperatae rhizoma and Hedyotis diffusa Willd. are herbs that are widely used as medicine and functional food. In traditional Chinese medicine theory, they are used as an herbal pair (HP) to treat inflammation-related diseases in the clinic, especially disorders of the kidney. PurposeThis study aimed to investigate the anti-inflammatory and hypolipidaemic effects of HP in an NS rat model and provide scientific data for its clinical application. MethodsAn NS model was established by two-dose injection of Sprague-Dawley rats with adriamycin. Seven groups, including the sham, model, HP treatment (0.25, 0.5 and 1.0 g/kg/d), prednisone (positive control, 5 mg/kg/d), and atorvastatin (positive control, 4 mg/kg/d) groups, were tested. The biochemical indexes of renal function and inflammatory cytokines were determined by ELISA kits and/or qPCR assays, and the crucial protein involved in the signalling pathway were subsequently tested by qPCR and/or Western blotting. Based on specific compounds identified by LC-Q-TOF-MS, network pharmacological study was carried out. ResultsThe levels of BUN, Scr, Upro, UA, Alb, TC, TG, and LDL-C were significantly elevated in model rats. HP treatment for four weeks improved the renal function and the dyslipidaemia by decreasing the levels of all parameters, except BUN and Scr. HP treatment (0.5 and 1.0 g/kg/d) upregulated the expression of PPARγ, CYP7b1, and LDLR in the liver, while it down-regulated PCSK9, showing a regulatory effect on lipid metabolism disorder. The levels of TNF-α and IL-1β in the plasma and the mRNA expression of TNF-α, IL-1β, MCP-1, and TGF-β1 in the kidney were decreased in HP groups, revealing its anti-inflammatory effect in NS rats. The HP exerted an alleviation effect on the inflammatory response through the NF-κB pathway by inhibiting the mRNA and protein expression of p50 and p65. There were 34 compounds identified or tentatively characterized in HP. In the network pharmacological study, PPARG(PPARγ), PCSK9, RELA(p65), and NF-κB1(p50) were the top 20 targets for HP, supporting the animal experimental results. Conclusion: HP exhibited protective effects on NS rats. These effects might be closely related to the inhibition of NF-κB and PCSK9-LDLR and activation of the PPARγ-CYP7B1 signalling pathways.

Corticosteroids Plus Intravenous Immunoglobulin Compared with Corticosteroids for the Treatment of Immune Thrombocytopenia in Pregnancy: An Observational Multicenter Study in China

Immune thrombocytopenia (ITP) affects 1-10 in 10,000 pregnancies (American College of Obstetricians and Gynecologists, et al. Int J Gynaecol Obstet. 1999). In contrast to ITP in nonpregnant individuals, treatment of ITP in pregnancy is limited and no consensus has been reached regarding treatment. Although corticosteroids and intravenous immunoglobulin (IVIg) are acceptable treatments for ITP in pregnancy, the evidence from large-scale clinical trials is still insufficient. Here we retrospectively analyzed the data from 5 collaborative centers in China to compare the effectiveness of corticosteroids plus IVIg with that of corticosteroids alone for the treatment of immune thrombocytopenia in pregnancy.Between January 2001 and July 2017, 521 women (572 pregnancies) were enrolled in this retrospective study. The diagnosis of ITP was confirmed in women previously diagnosed with ITP. Patients whose platelet counts remained above 70×109/L during pregnancy and normalized in the postpartum period were deemed to have gestational thrombocytopenia and were excluded (Sun D, et al. Blood 2016). The median initial prednisone dose was 15 mg/d (interquartile range [IQR] 10-30 mg/d) in both the combined therapy group and the monotherapy group. IVIg was given concomitantly at a daily dose of 20g during the first 3-5 days in the combined therapy group. Another 3 cycles of IVIg were given every 2-4 weeks if maternal platelet response was observed (platelets ≥30×109/L). Withdrawal of IVIg could be performed when platelets rose above 300×109/L in <14 days. A total of 2 cycles of IVIg could be given for no platelet response (platelets <30×109/L).The intervention was not introduced in 340 pregnancies (340/572, 59%). Among the remaining 232 women with pregnancies, 105 (45%) were given prednisone plus IVIg as the initial treatment and 127 were given only prednisone. The maternal characteristics, including age, maternal pretreatment platelet count, bleeding score and more, did not differ between the two groups. No differences between the two groups were observed with regard to the maternal response to the initial treatment (including complete response [CR] and partial response [PR], prednisone plus IVIg 48% vs. prednisone 36%, p=0.08), nor were differences observed with regard to the proportion of maternal complications, including bleeding episodes in the antenatal period, platelet count at delivery, pre-delivery platelet transfusion, mode of delivery (vaginal delivery or cesarean section), abortion and premature delivery. For patients with an initial response, there was a significant difference between the time to response (TTR) of the corticosteroids plus IVIg group (median and range, 3 and 1-14 days) and the TTR of the corticosteroid group (7 and 2-18 days) (p <0.01). Notably, 62 of 81 pregnancies with no response to prednisone were given IVIg, and the response to the treatment was 34% (21/62). Moreover, of 324 women (357 pregnancies) with a history of ITP, the majority of pregnancies (255/357, 71%) did not require treatment. A review of 197 women (215 pregnancies) with newly diagnosed ITP during pregnancy revealed that most ITP (161/215, 74.8%) was first recognized in the first trimester. With regard to the neonatal characteristics, 599 neonates (572 pregnancies) were live births and none were intrauterine death. Among 389 neonates (389/599, 65%) whose cord blood platelet counts were measured, platelet counts<100×109/L were observed in 118/389 (30%) neonates, and specifically in 18/155 neonates (12%) whose mothers were not treated. No fatal or severe neonatal hemorrhage was observed. The proportion of neonates with an Apgar score <7 at 5 minutes and neonatal platelet counts at birth did not differ between the groups. Neonatal cord platelet count compared with maternal platelet count at delivery indicated a lack of linear relation. Adverse events, including hyperglycemia requiring treatment, infection, and others, were reported in 19/105 (18%) of the prednisone plus IVIg group and in 31/127 (24%) of the prednisone group (p=0.28).In conclusion, no better maternal platelet count response but a shorter TTR were shown in the prednisone plus IVIg group compared with the prednisone group in this observational study of ITP patients in pregnancy. Prospective studies are needed to better identify the effectiveness and safety of these regimens and to explore new therapeutic options. DisclosuresNo relevant conflicts of interest to declare.