Mean Cumulative Dose Of Prednisone Research Articles

Treatment of idiopathic nephrotic syndrome at onset: a comparison between 8- and 12-week regimens in everyday clinical practice.

Optimal steroid treatment at onset of idiopathic nephrotic syndrome is still debated. The aim of this study was to analyze the clinical outcome at 24months of follow-up in patients admitted to our unit for the first episode of steroid-sensitive nephrotic syndrome comparing two different steroid regimens. We collected data on patients treated from 1992 to 2007 with prednisone according to the International Study on Kidney Diseases in Children 8-week regimen and since 2008 according to the Arbeitsgemeinschaft fur Padiatrische Nephrologie 12-week regimen. The primary outcome was to evaluate cumulative prednisone dosage at 12 and 24months of follow-up in the two groups. As secondary outcomes, we considered mean relapse rate per patient; number of children without relapses at 6, 12, and 24months; and number of patients who developed frequent relapses and steroid-dependent disease. Data were collected on 127 patients. Sixty-one subjects received the 8-week regimen and 66 the 12-week regimen. The mean cumulative prednisone dose at 12 and 24months was not different, and the rate of patients without relapses was lower at 6 and 12months in patients treated with the 8-week course, while no difference was observed at 24months. Despite the limitations of a retrospective study with limited follow-up, our data indicate that switching treatment from a shorter to a longer scheme did not improve the clinical outcome at 24months of observation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of Steroid Treatment on the Diagnostic Yield of Baseline PET CT in Aggressive B Cell Lymphoma

Aggressive B cell lymphomas often require prompt steroid treatment prior to baseline 18f-fluorodeoxyglucose positron-emission tomography (PET CT) scan and definitive treatment in order to alleviate symptoms and/or prevent organ damage. Since lymphomas are a steroid sensitive malignancy, there is a concern that steroid prophase might affect PET CT results and diagnostic yield.We conducted a retrospective cohort study to evaluate the effect of steroid treatment prior to baseline PET CT scan on the standardized uptake value (SUV) max and additional PET CT parameters by examining two groups of patients: steroid-naïve and steroid-treated patients. The effect of steroid administration on SUV max was examined across different daily and weekly steroid doses and durations of treatment.Between January of 2017 and May 2020, 187 newly diagnosed patients with aggressive B cell lymphoma who had a pre-treatment PET CT scan were evaluated. 160 patients (85.5%) had Diffuse large B-cell lymphoma (DLBCL)/ High-grade B-cell lymphoma, 13 patients (7%) had primary mediastinal (thymic) large B-cell lymphoma, 9 patients (4.8%) had primary DLBCL of the central nervous system and 5 patients (2.7%) had Burkitt lymphoma.132 patients (70.6%) were included in the steroid-naïve group and 55 patients (29.4%) in the steroid-treated group. In the steroid-treated group, the mean duration of steroid treatment was 10.49 (±9.28) days. Average daily dose of steroid treatment was equivalent to 72.27 (±36) mg of prednisone and the mean cumulative prednisone dose during the week prior to PET CT scan was equivalent to 367.95 (±239.9) mg of prednisone.There was no statistical significant difference between the groups in age, gender or KI67. However, patients in the steroid treated group had a significantly higher stage of disease compared to the steroid-naïve group (mean 3.44 compared to 2.99, respectively, p=0.01). The steroid-treated group also had a trend towards a higher IPI score (mean 2.45 versus 2.08, p=0.08) and a trend towards a higher LDH level (mean 2309.89 U/L, range 250-81374 versus mean 877.65 U/L, range 272-22036, p= 0.07), as depicted in table 1.There was no statistical difference in SUV max between the steroid-naïve and steroid-treated groups (p=0.97). This was consistent across various steroid treatment durations and dosage regimes. Patients in the steroid-treated group had a trend towards a higher tumor burden and a larger tumor volume compared to the steroid-naïve group, however it did not reach statistical significance. Mean tumor volume was 179.04 cm 3 in the steroid naïve group and 337.06 cm 3 in the steroid treated group (p=0.17). Mean tumor burden was 1944.84 in the steroid-naïve group and 3016.94 in the steroid-treated group (p=0.09).There was no difference in additional PET CT parameters including SUV mean, SUV max and SUV mean of liver and mediastinum between the groups as depicted in table 2.In conclusion, in aggressive B cell lymphoma, pre-treatment with steroids prior to initial PET CT scan does not affect SUV max or other PET CT parameters and does not reduce PET CT diagnostic yield. [Display omitted] DisclosuresGurion: Medison: Consultancy; Gilead Sciences: Consultancy; Takeda Pharmaceuticals: Consultancy; JC Health Care: Honoraria; Roche: Honoraria.

Belimumab for the treatment of children with frequently relapsing nephrotic syndrome: the BELNEPH study.

Effectiveness of rituximab in pediatric idiopathic nephrotic syndrome suggests that B cells play a pathogenic role. We tested safety and efficacy of the B-cell-modulating agent belimumab in frequently relapsing nephrotic syndrome (FRNS). An open-label, prospective, single-arm pilot study (EUDRACT 2017-003839-11) was designed to treat 10 children with FRNS with i.v. belimumab for 12 months. Prednisone was tapered/stopped. Safety, number of relapses, cumulative prednisone dose and B-cell subset "levels" are referred to both B cell subset and immunoglobulin. Five patients were enrolled, and four reached the primary 6-month endpoint. Of these, two completed the 12-month endpoint. Three patients experienced ≥2 relapses while on belimumab, requiring additional immunosuppression. Compared to the 6 months before belimumab treatment, the mean number of relapses (1.4 vs. 2, p=0.21) and the mean cumulative prednisone dose (1.86 vs. 2.62 g/m2, p=0.17) were not significantly reduced during the 6 months on belimumab. This study was terminated by the steering committee after the interim evaluation because belimumab failed to show clear benefits to counterbalance the inconvenience of monthly i.v. infusion. During follow-up, total and mature-naïve B cells decreased, while no change in memory B-cells was observed. Serum immunoglobulins remained stable. No infusion reaction was observed. Short-term treatment with belimumab in pediatric FRNS was well tolerated. The number of patients was too small to draw conclusions on efficacy. Nonetheless, we did not observe clear improvements. The burden of monthly in-hospital i.v. infusions outweighed potential benefits. Persistence of circulating memory B cells supports their pathogenic role in the disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis.

To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6-4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P=0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P=0.007), CVDs (7.9%, P=0.001) and severe infections (9.9%, P=0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. (ClinicalTrials.gov Identifier: NCT03666091).

P0399RELAPSE TREATMENT WITH LOW DOSE OF STEROIDS IN STEROID-SENSITIVE MINIMAL CHANGE DISEASE

Abstract Background and Aims Treatment of Minimal change disease (MCD) consists of high dose of steroids (HDS) for several weeks implying significant drug toxicity. On the other hand, renal relapses of steroid-sensitive MCD sometimes respond to lower doses of steroids. Method The objective of the study was to analyze weather low dose for steroids (LDS) is effective for treatment MCD relapses among frequently-relapsing steroid-sensitive patients. Since 2019, new relapses of steroid-sensitive patients with MCD within the Nephrology Department of Hospital Ramón y Cajal were treated with LDS. Cumulative dose of steroids, time to remission and time free of relapse were compared between relapse episodes treated with LDS and previous relapses among same patients treated with HDS. Results Twenty-six relapses among six steroid-sensitive MCD patients were analyzed. 15 relapses were treated with LDS and compared with 11 previous relapses among same patients treated with HDS. Mean dose of prednisone for initial treatment of the relapse was 0.89 ± 0.1 mg/kg in patients treated with HDS and 0.45 ± 0.1 mg/kg in patients treated with LDS. Mean cumulative dose of prednisone among patients treated with LDS and HSD were 1998.1 ± 1418 mg and 5611.7 ± 2326 mg, respectively. (p=0.001). Mean cumulative dose of prednisone adjusted by body weight among patients treated with LDS and HSD were 23.43 ± 14.27 mg/kg and 68.93 ± 27.05 mg/kg, respectively. (p=0.019). There was no difference in duration of treatment among HDS and LSD groups (163.45 ± 86.43 vs 138.80 ± 108.80, respectively; p = 0.525). All patients achieved complete remission after steroid therapy in both LSD and HSD groups. Mean time to remission was 18.7 days among HSD relapses and 18.4 days among the LSD relapses (p = 0.9). Time free of relapse after therapy among HDS and LDS treated relapses was 9.1 ± 5.3 months and 5.5 ± 3.5 months, respectively (p = 0.1). Conclusion Among steroid-sensitive MCD patients, relapse therapy with low dose of steroids (0.5 mg/kg) seems to be effective and allows minimization of steroid cumulative dose and drug toxicity.

Avascular necrosis after chemotherapy for haematological malignancy in childhood

Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin's lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011. Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. Time to next exacerbation within 180 days. Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD. isrctn.org Identifier: ISRCTN19646069.

THU0330 Damage in juvenile-onset systemic lupus erythematosus

BackgroundChildren and adolescents with juvenile-onset systemic lupus erythematosus (jSLE) face considerable morbidity due to sequelae of disease activity, comorbidities and adverse effects of treatment. In order to improve the management...

Final height of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome

The aim of this study was to evaluate the final stature of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome (INS) and the influence of disease-related issues on the achievement of their target heights. We analyzed 60 (41 male) patients and/or their records, with a minimum age of 19 years or at a Tanner's pubertal stage 4 for boys or status postmenarche for girls, and normal glomerular filtration rate. Mean age at first and last consultation was 5.3+/-2.4 years and 20.5+/-3.1 years, respectively. Mean follow-up period was 15.10 years. Mean cumulative dose of prednisone was 1254+/-831.40 mg/kg. Mean initial and final height Z scores (HtZ) were, respectively, -0.60+/-1.0 and -0.64+/-0.92 (p=0.72). The final HtZ showed a significant correlation only with the initial HtZ and the target HtZ (THZ). Six patients achieved a final HtZ below -2, which in male patients correlated strongly to the initial HtZ and THZ. A strong correlation was demonstrated between final HtZ, initial HtZ, and THZ. INS-related issues did not prevent the final stature to reach the predicted target height.

EVALUATION OF BONE MINERAL DENSITY AT DIFFERENT PHASES OF THERAPY OF CHILDHOOD ALL

In the present study the authors evaluated the status of spinal bone mineral density (BMD) using dual-energy X-ray absorptiometry in a group of 31 children with acute lymphoblastic leukemia, treated by ALL-BFM protocols without irradiation, at different phases of their treatment. These patients were studied (1) within 2 months of diagnosis (group 1, n = 17, median time postdiagnosis 17 days), (2) during chemotherapy (group 2, n = 16, median time on treatment 22 months), and (3) shortly after completion of therapy (group 3, n = 10, median time postchemotherapy 13 months). Twelve patients underwent serial measurements in either of the groups they entered (6 patients of group 1 and 6 patients of group 2). The mean cumulative prednisone dose was 0.8, 4.3, and 5 g/m2 in groups 1, 2, and 3, respectively. A gradual decline of BMD from group 1 through group 3 was observed. The mean value of age- and sex-specific BMD z-score was −0.74 (±0.32) in group 1, −1.59 (±0.24) in group 2, and −2.03 (±0.27) in group 3; there was a statistically significant difference between groups 1 and 3 (p =. 022). A BMD z-score < −2 was found in 3 (17%), 4 (25%), and 5 (50%) patients of groups 1, 2, and 3, respectively. In conclusion, a high incidence of reduced bone mass was observed during and shortly after treatment. These findings could have significant consequences in long-term survivors.

Prevention of cancellous bone loss but persistence of renal bone disease despite normal 1,25 vitamin D levels two years after kidney transplantation.

Osteopenia has been observed to occur frequently after renal transplantation. The present study was undertaken to assess whether an immunosuppressive regimen combining cyclosporine with no or the lowest possible maintenance doses of glucocorticoid may prevent osteopenia after kidney transplantation. Thirty-four patients were prospectively followed for two years. Serial blood drawings were done for determination of serum indices of calcium and bone metabolism and an iliac crest bone biopsy was performed at time of transplantation. A second bone biopsy was done in 20 patients during the second year of observation. Creatinine clearance was 56 +/- 6 ml/min one year and 46 +/- 6 ml/min two years after transplantation. Serum parathyroid hormone levels were elevated in 24 patients at time of grafting, decreased significantly thereafter, but remained above the normal range. Ten patients had low or normal serum parathyroid hormone levels at time of transplantation and showed a significant increase after grafting. Two years after transplantation, the mean cumulative dose of prednisone was 5.9 +/- 0.5 g. After the first six months, 30-40% of the patients were not on maintenance doses of steroids. None of the patients experienced fractures, and cancellous bone volume was within or above the normal range in all repeat bone biopsies. It is of note that metabolic bone abnormalities did not resolve 1-2 years after transplantation despite normalization of serum 1,25 vitamin D levels. The histologic abnormalities at the time were consistent with the bone findings in renal failure suggesting resistance of bone to normal circulating levels of 1,25 vitamin D.

Methotrexate Treatment in the Management of Giant Cell Arterirtis

Eleven newly-diagnosed GCA patients were included in a prospective open study and treated with high initial prednisone doses, a quick-tapering CS schedule and weekly oral MTX for two years. It took a mean of 14 weeks to reach a 10 mg/day dose of prednisone and 29.8 weeks until steroid withdrawal. The mean cumulative dose of prednisone was 3.4 g. Two patients relapsed and five developed CS side effects. No serious MTX side effects were observed. Our results suggest that MTX is safe and could be useful in the therapy of GCA.