Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.

BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

OBJECTIVES: For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab. METHODS: This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks. RESULTS: Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). CONCLUSIONS: Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

Evaluation of the effectiveness of using prednisolone, tacrolimus, and intravenous immunoglobulin combination therapy on immune-mediated necrotizing myopathy-A non-randomized, observational research.

OBJECTIVE: To recruit immune-mediated necrotizing myopathy (IMNM) patients with extramuscular manifestations who were refractory to initial therapy with either monotherapy with prednisolone or dual therapy with prednisolone and immunosuppressants. These patients subsequently received a combination of prednisolone, tacrolimus, and intravenous immunoglobulin (IVIG), and the efficacy of this treatment regimen was assessed in patients with IMNM. METHOD: ①Clinical data and treatment measures are as follows: This study enrolled IMNM patients who were treated at the Neurology Department of the First Medical Center of PLA General Hospital from April 2020 to May 2023. These patients received a combination therapy of prednisolone, tacrolimus, and IVIG. ②Observational indicators included manual muscle test for 8 groups of muscles (MMT-8), muscle enzyme levels (creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST)), and myositis disease activity assessment tool (MDAAT). RESULTS: This study enrolled eight patients. All observational indicators declined after treatment compared to before treatment, and these changes were statistically significant. Moreover, extramuscular manifestations also ameliorated compared to before treatment. CONCLUSION: The combination therapy of prednisolone, tacrolimus, and IVIG has demonstrated favorable efficacy in IMNM and broadened the treatment options for this disease. However, the results still require further validation by large-scale and randomized controlled studies.

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Bone quality in zebrafish vertebrae improves after alendronate administration in a glucocorticoid-induced osteoporosis model.

Glucocorticoid-induced osteoporosis (GIOP) changes the microarchitecture of bones and often leads to the reduction of bone-mineral density (BMD) and increased fracture rates. Zebrafish has been used as an alternative model for GIOP, however, the interaction of GIOP, and its treatment, with zebrafish bone morphometrics and mechanical properties, remains a challenge. Thus, this study aimed to evaluate the effects of prednisolone and alendronate on the properties of zebrafish vertebrae. Adult 7-month-old zebrafish were distributed into four groups: control (CTRL), prednisolone-only (PN), alendronate-only (ALN), and the sequential use of both medicines (PN + ALN). Fish skeletons were scanned via micro-tomography (n = 3) to obtain vertebra morphometrics (e.g., BMD). Bone morphology was assessed using scanning electron microscopy (n = 4) and the biomechanical behaviour with nanoindentation technique (n = 3). The BMD decreased in PN (426.08 ± 18.58 mg/cm3) and ALN (398.23 ± 10.20 mg/cm3) groups compared to the CTRL (490.43 ± 41.96 mg/cm3) (p < 0.001); however, administering the medicines in sequence recovered the values to healthy levels (495.43 ± 22.06 mg/cm3) (p > 0.05). The bone layered structures remain preserved in all groups. The vertebrae of the groups that received ALN and PN + ALN, displayed higher modulus of elasticity (27.27 ± 1.59 GPa and 25.68 ± 2.07 GPa, respectively) than the CTRL (22.74 ± 1.60 GP) (p < 0.001). ALN alone increased the hardness of zebrafish vertebrae to the highest value among the treatments (1.32 ± 0.13 GPa) (p < 0.001). Conversely, PN + ALN (1.25 ± 0.11 GPa) showed unaltered hardness from the CTRL (1.18 ± 0.13 GPa), but significantly higher than the PN group (1.08 ± 0.12 GPa) (p < 0.001). ALN administered after GIOP development, rescued osteoporotic condition by recovering the BMD and bone hardness in zebrafish vertebrae.

An open label non-inferiority randomized controlled trial evaluated alternate day prednisolone given daily during infections vs. levamisole in frequently relapsing nephrotic syndrome.

Initial therapies for children with frequently relapsing nephrotic syndrome include alternate-day prednisolone that is given daily during infections, or levamisole. In this open label, non-inferiority trial, 160 patients, 2 to 18-years-old with frequent relapses, were randomly assigned to receive either prednisolone (0.5-0.7 mg/kg/alternate-day, given daily during infections), or levamisole (2-2.5 mg/kg/alternate-days) for one-year. Patients with relapses on alternate day prednisolone at over 1 mg/kg, prior use of potent steroid-sparing therapies, eGFR under 60 ml/min/1.73 m2 and significant steroid toxicity were excluded. Primary outcome was the proportion of patients with frequent relapses, defined as three-relapses in one-year, or two-relapses within six-months if associated with significant steroid toxicity or loss to follow up. Eighty patients each were randomized to receive prednisolone and levamisole. Baseline features showed preponderance of young patients presenting within two-years of disease onset. On intention-to-treat analysis, frequent relapses were more common in patients administered prednisolone (40% versus 22.5%; risk difference 17.5%; 95% confidence interval 3.4-31.6%). Prednisolone was not non-inferior to levamisole in preventing frequent relapses. However, the two groups showed similar proportions of patients in sustained remission, comparable frequency of relapses, and low frequency of adverse events. The decline in steroid requirement from baseline was higher in the levamisole group. Per-protocol analysis showed similar results. These results have implications for choice of therapy for frequently relapsing nephrotic syndrome. Although therapy with alternate-day prednisolone was not non-inferior to levamisole in preventing frequent relapses, both therapies were effective in other outcome measures. Thus, levamisole was relatively steroid-sparing and may be preferred in patients at risk of steroid toxicity.

Effect of prednisolone for the treatment of medication-overuse headache: A 3-month result from a multicenter REgistry for Load and management of mEdicAtion overuSE headache (RELEASE) study.

OBJECTIVE: To evaluate the efficacy of prednisolone in the treatment of medication-overuse headache (MOH) using data from a multicenter prospective registry (Registry for Load and Management of Medication Overuse Headache [RELEASE]). BACKGROUND: The treatment of MOH is challenging, especially when withdrawal headache manifests during the cessation of overused medication. Although systemic corticosteroids have been empirically used to reduce withdrawal headaches, their efficacy on the long-term outcomes of MOH has not been documented. METHODS: This was a post hoc analysis of the RELEASE study. The RELEASE is an ongoing multicenter observational cohort study in which patients with MOH have been recruited from seven hospitals in Korea since April 2020. Clinical characteristics, disease profiles, treatments, and outcomes were assessed at baseline and specific time points. We analyzed the effect of prednisolone on MOH reversal at 3 months. RESULTS: Among the 309 patients enrolled during the study period, prednisolone was prescribed to 59/309 (19.1%) patients at a dose ranging from 10 to 40 mg/day for 5-14 days; 228/309 patients (73.8%) completed the 3-month follow-up period. The MOH reversal rates at 3 months after baseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the non-prednisolone group (p = 0.034). The effect of steroids remained significant (adjusted odds ratio 2.78, 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of preventive medications combined. CONCLUSIONS: Although our observational study could not draw a definitive conclusion, prednisolone may be effective in the treatment of MOH.

Cryptogenic organizing pneumonia after withdrawal of systemic corticosteroids for chronic eosinophilic pneumonia and severe asthma under benralizumab treatment.

A 79-year-old woman with severe asthma developed chronic eosinophilic pneumonia (CEP). After CEP resolved with oral prednisolone at 30 mg/day, prednisolone was tapered and discontinued under introduction of benralizumab for her severe asthma. However, 8 weeks later, symptoms and bilateral patchy infiltrates on chest radiography appeared. Lymphocytosis without eosinophilia was seen in bronchoalveolar lavage fluids, and transbronchial biopsy indicated organizing pneumonia. Cryptogenic organizing pneumonia (COP) was diagnosed and resolved with prednisolone at 30 mg/day. Prednisolone was tapered to 3 mg/day without relapse of CEP or COP. This case suggests the overlap and similar pathogenesis of CEP and COP.

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.

BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. METHODS: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. RESULTS: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). CONCLUSIONS: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. IMPACT AND IMPLICATIONS: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. TRIAL REGISTRATION NUMBER: #NCT02900443.

Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial.

INTRODUCTION: Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. PATIENTS AND METHODS: This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. RESULTS: The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. CONCLUSIONS: The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.KEY MESSAGESLow initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double-blind, efficacy, and safety study.

Oral corticosteroid use is limited by side effects, some caused by off-target actions on the mineralocorticoid receptor that disrupt electrolyte balance. AZD9567 is a selective, nonsteroidal glucocorticoid receptor modulator. The efficacy, safety, and tolerability of AZD9567 and prednisolone were assessed in a phase IIa study. Anti-inflammatory mechanism of action was also evaluated in vitro in monocytes from healthy donors. In this randomized, double-blind, parallel-group, multicenter study, patients with active rheumatoid arthritis were randomized 1:1 to AZD9567 40 mg or prednisolone 20 mg once daily orally for 14 days. The primary end point was change from baseline in DAS28-CRP at day 15. Secondary end points included components of DAS28-CRP, American College of Rheumatology (ACR) response criteria (ACR20, ACR50, and ACR70), and safety end points, including serum electrolytes. Overall, 21 patients were randomized to AZD9567 (n = 11) or prednisolone (n = 10), and all completed the study. As anticipated, AZD9567 had a similar efficacy profile to prednisolone, with no clinically meaningful (i.e., >1.0) difference in change from baseline to day 15 in DAS28-CRP between AZD9567 and prednisolone (least-squares mean difference: 0.47, 95% confidence interval: -0.49 to 1.43). Similar results were observed for the secondary efficacy end points. In vitro transcriptomic analysis showed that anti-inflammatory responses were similar for AZD9567, prednisolone, and dexamethasone. Unlike prednisolone, AZD9567 had no effect on the serum sodium:potassium ratio. The safety profile was not different from that of prednisolone. Larger studies of longer duration are required to determine whether AZD9567 40 mg may in the future be an alternative to prednisolone in patients with inflammatory disease.

Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial.

Importance: Many patients 65 years or older with metastatic castration-resistant prostate cancer (mCRPC) are denied taxane chemotherapy because this treatment is considered unsuitable. Objective: To determine whether biweekly cabazitaxel (CBZ), 16 mg/m2 (biweekly CBZ16), plus prophylactic granulocyte colony-stimulating factor (G-CSF) at each cycle reduces the risk of grade 3 or higher neutropenia and/or neutropenic complications (eg, febrile neutropenia, neutropenic infection, or sepsis) compared with triweekly CBZ, 25 mg/m2 (triweekly CBZ25), plus G-CSF (standard regimen). Design, Setting, and Participants: A total of 196 patients 65 years or older with progressive mCRPC were enrolled in this prospective phase 3 randomized clinical trial conducted in France (18 centers) and Germany (7 centers) between May 5, 2017, and January 7, 2021. All patients had received docetaxel and at least 1 novel androgen receptor-targeted agent. Interventions: Patients were randomly assigned 1:1 to receive biweekly CBZ16 plus G-CSF and daily prednisolone (experimental group) or triweekly CBZ25 plus G-CSF and daily prednisolone (control group). Main Outcome and Measures: The primary end point was the occurrence of grade 3 or higher neutropenia measured at nadir and/or neutropenic complications. Results: Among 196 patients (97 in the triweekly CBZ25 group and 99 in the biweekly CBZ16 group), the median (IQR) age was 74.6 (70.4-79.3) years, and 181 (92.3%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median (IQR) follow-up duration was 31.3 (22.5-37.5) months. Relative dose intensities were comparable between groups (median [IQR], 92.7% [83.7%-98.9%] in the triweekly CBZ25 group vs 92.8% [87.0%-98.9%] in the biweekly CBZ16 group). The rate of grade 3 or higher neutropenia and/or neutropenic complications was significantly higher with triweekly CBZ25 vs biweekly CBZ16 (60 of 96 [62.5%] vs 5 of 98 [5.1%]; odds ratio, 0.03; 95% CI, 0.01-0.08; P < .001). Grade 3 or higher adverse events were more common with triweekly CBZ25 (70 of 96 [72.9%]) vs biweekly CBZ16 (55 of 98 [56.1%]). One patient (triweekly CBZ25 group) died of a neutropenic complication. Conclusions and Relevance: In this randomized clinical trial, compared with the standard regimen, biweekly CBZ16 plus G-CSF significantly reduced by 12-fold the occurrence of grade 3 or higher neutropenia and/or neutropenic complications, with comparable clinical outcomes. The findings suggest that biweekly CBZ16 regimen should be offered to patients 65 years or older with mCRPC for whom the standard regimen is unsuitable. Trial Registration: ClinicalTrials.gov Identifier: NCT02961257.

In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs.

BACKGROUND: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain. AIMS: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date. METHODS: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses. RESULTS: D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01). CONCLUSIONS: Incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.

Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design.

BACKGROUND: Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen. METHODS: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients' global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed. DISCUSSION: This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680.

Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature.

OBJECTIVE: To evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth. DESIGN: Four DMD patients on Deflzacort 0.6-0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6-18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD). RESULTS: Growth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3-7.8 cm/year over a period of 6-18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment. CONCLUSIONS: rhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.

Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial.

OBJECTIVE: The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication. METHODS: Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering. RESULTS: 191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit -0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency. CONCLUSIONS: Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration.

Effect of early initiation of steroid-sparing drugs in patients with bullous pemphigoid.

Introduction: Bullous pemphigoid (BP) can be treated using systemic and topical glucocorticoids and/or other immunomodulatory agents. However, the long-term use of systemic glucocorticoids causes severe adverse side effects. This study was aimed at investigating whether the early initiation of corticosteroid-sparing therapy (CST) in BP patients results in better outcomes than late or no CST. Method: We retrospectively identified all BP patients referred to the tertiary center, of the Department of Dermatology and Venerology, Aarhus University Hospital, Denmark, from 2015 to 2021. Patients' demographics, comorbidities, treatment, remission of BP, length of admission, relapse, and 1-year mortality were recorded. All patients who received CST were dichotomised into two groups: initiated with CST <28 or >28 days. The groups were compared using t-tests. Additionally, all patients who received CST were compared with those who received systemic glucocorticoids alone. Our cohort was compared with that of a previous study (2006-2013) performed in our department. In 2015, we revised our BP treatment guidelines to include the early initiation of CST. Results: On comparing the group of patients initiated with CST <28 versus >28 days, we found no significant differences in the complications or mortality between the groups (p = 0.63 and p=0.79, respectively). The <28 days group had a lower rate of relapse (p < 0.05). On comparing data from this study with those from the previous study, conducted before we revised our treatment guideline, we found a reduced initial dose of prednisolone and reduced admission time in this study. No significant differences were found between patients treated with CST and those treated with systemic glucocorticoids alone. Conclusion: The rate of complications and 1-year mortality did not differ significantly between the two subgroups in this study. The relapse rate was lower in the CST <28 days group than in the CST >28 days group. The initial dose of prednisolone and admission time were reduced in this study compared with those in the previous study performed before the implementation of a local treatment guideline recommending the early initiation of CST.

Time and dose-dependent effect of systemic glucocorticoids on major adverse cardiovascular event in patients with rheumatoid arthritis: a population-based study.

OBJECTIVES: Cardiovascular event (CVE) risk in rheumatoid arthritis (RA) was increased by glucocorticoids (GC) use. Whether there is a threshold dose and duration of GC use beyond which will increase CVE rate remains controversial. We studied the time-varying effect of GC and its dose on the risk of incident major adverse cardiovascular events (MACE) in patients with RA. METHODS: Patients with RA without MACE at baseline were recruited from a Hong Kong citywide database from 2006 to 2015 and followed till 2018. The primary outcome was the first occurrence of an MACE. Cox regression and inverse probability treatment weighting analyses with time-varying covariates were used to evaluate the association of GC and MACE, adjusting for demographics, traditional CV risk factors, inflammatory markers and the usage of antirheumatic drugs. RESULTS: Among 12 233 RA patients with 105 826 patient-years of follow-up and a mean follow-up duration of 8.7 years, 860 (7.0%) developed MACE. In the time-varying analyses after controlling for confounding factors, a daily prednisolone dose of ≥5 mg significantly increased the risk of MACE (erythrocyte sedimentation rate model: HR 2.02, 95% CI 1.72 to 2.37; C reactive protein model: HR 1.87, 95% CI 1.60 to 2.18), while a daily dose below 5 mg was not associated with MACE risk, compared with no GC use. In patients receiving daily prednisolone ≥5 mg, the risk of incident MACE was increased by 7% per month. CONCLUSIONS: GC was associated with a duration and dose-dependent increased risk of MACE in patients with RA. Very low dose prednisolone (<5 mg daily) did not appear to confer excessive CV risk.

Single- versus Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children: An Open-Label RCT.

BACKGROUND: Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has resulted in variation in practice, with divided-dose prednisolone still commonly used. We conducted this open-label randomized control trial to compare HPA axis suppression between single-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome. METHODS: Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl. RESULTS: Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002. CONCLUSIONS: Among children with first episode of nephrotic syndrome, single-dose and/or divided-dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CTRI/2021/11/037940. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000216.mp3.

Rituximab in the management of retroperitoneal fibrosis: A single tertiary rheumatology care center experience.

AIM: To investigate the clinical and radiological outcomes and glucocorticoid-sparing effect of rituximab therapy in 13 patients with retroperitoneal fibrosis (RPF). METHODS: We analyzed the data of both glucocorticoid-naive and glucocorticoid-resistant RPF patients who were treated with rituximab. Demographic features, positron emission tomography computed tomography (PET-CT) findings, and clinical and histopathologic outcomes were collected retrospectively. RESULTS: We evaluated the data of 13 RPF patients (8M/5F). The median follow-up duration was 28 months (interquartile range [IQR] 24.5-55.5 months) and median age at the time of diagnosis was 50.8 years (IQR 46.5-54.5 years). PET-CT scans showed that following the rituximab therapy, the craniocaudal diameter of the RPF mass reduced from 74 mm (IQR 50.5-130 mm) to 52 mm (IQR 35-77 mm; p = .06), and periaortic thickness of the RPF mass reduced from 14 mm (5.5-21.9 mm) to 7 mm (4.5-11 mm; p = .12). The maximum standardized uptake value (based on body weight) of the RPF mass decreased from 5.8 (4.3-9.7) to 3.1 (2.8-5.3) after the therapy (p = .03). The number of patients with hydronephrosis reduced from 11 to 6 following rituximab therapy (p = .04). Before rituximab, nine patients received a median dose of 10 mg (IQR 0-27.5 mg) prednisolone per day. After the rituximab treatment, we discontinued prednisolone treatment for four out of nine patients and reduced the daily dose for the remaining patients. At the time of the final evaluation of the patients, the median prescribed prednisolone dose was 5 mg/day (IQR 2.5-7.5 mg/day; p = .01). CONCLUSION: Our study shows that rituximab may be a favorable treatment option for glucocorticoid-refractory RPF patients with high disease activity on PET-CT scans.