Cumulative Corticosteroid Dose Research Articles

#6660 HERPES ZOSTER IN LUPUS NEPHRITIS: AN UNDERESTIMATED COMPLICATION

Abstract Background and Aims Herpes zoster (HZ) is a known complication of lupus nephritis (LN) because of the drug-related immunosuppression. In fact, high dose corticosteroids (CS) and immunosuppressive (IS) therapy are almost always used in this setting. Our aim is to evaluate the predisposing factors for the development of HZ in patients with LN. Method Retrospective cohort study on 292 LN patients. Demographic and clinical data are expressed as numbers or percentages in case of discrete variables, whereas, in case of continuous variables, they are expressed as median and interquartile range (IQR). The demographic characteristics have been analyzed with Mann-Whitney U test and Fisher's test where appropriated. A univariate and multivariate logistic regression has been performed to identify potential risk factors. Results The incidence of HZ in our cohort is 22.6% (66/226). The patients’ characteristics are shown in Table 1. HZ patients are older (54 vs 45 yo, p<0.001). No differences were found in the clinical characteristics at LN diagnosis, except for higher chronicity index in HZ patients (2 vs 1, p = 0.03). No difference was found in the initial IS therapy. Higher cumulative dose of CS was used in patients with HZ (48.9 vs 21.5 grams, p<0.0001). At univariate and multivariate logistic regression (Table 2) age, female sex, the presence of a proliferative form at renal biopsy (class III or IV) and cumulative CS dose greater than 100 grams are linked to a higher risk for HZ. Conclusion Incidence of HZ in our LN cohort is high (22.6%). HZ patients are older, while non-significative differences in clinical presentation or initial IS therapy are present. Age, female sex, the presence of a proliferative form at biopsy and greater cumulative CS dose seems to be a risk factor for HZ development in LN patients. According to these data and to the possible evolution of HZ infection in disseminated forms, HZ vaccination should be strongly recommended in LN patients.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: Axi-cel was approved by NMPA to treat R/R LBCL adult patients who had received 2 or more prior treatments in 2021 June. For better understanding the efficacy and safety of commercial Axi-cel in Chinese R/R NHL patients in real world setting, we conducted this multi-center, non-interventional study (ChiCTR2100047990). The accrual goal is 200 patients, and the primary endpoint is median OS. Here we made an interim analysis and reported clinical outcomes of Chinese patients treated by commercial CAR-T products in real world for the first time. Methods: R/R NHL patients treated with commercial Axi-cel in 17 authorized treatment centers from 11/2021 to 02/2023 were included. All patients signed written informed consents. We reported best objective response rate (bORR), best complete response (bCR) rate and adverse events. Results: A total of 101 R/R NHL patients were efficacy-evaluable. The median age was 56.8 years old, and 25 (24.8%) patients were ≥65 years. Fifty-nine patients were male. Baseline characteristics, including 80 (79.2%) with DLBCL, 4 (4.0%) with PMBCL, and 6 (5.9%) with high grade B-cell lymphoma. Forty-two (44.2%) patients had IPI ≥3 and 18 (24.3%) patients ECOG PS were ≥2. The median prior lines of therapy was 2, including 36 (35.6%) patients got ≥3 previous treatments and 10 patients had history of ASCT. Eighty-four patients were resistant to previous therapy, and the primary refractory subgroup reached 47 (46.5%). Bridging therapy was given in 56 (55.4%) patients, while combination therapy in 29 (28.7%) patients. The median follow-up was 9.2 months. The bORR and bCR was 83.2% (95% CI, 74.4 to 89.9) and 58.4% (95% CI, 48.2 to 68.1) respectively (Figure 1A). Response rates were consistent across key covariates, including disease type, disease stage, IPI score, cell-of-origin subtype, etc. Patients ≥65 years had favorable ORR [92.0% (95% CI, 74.0–99.0)] and CR rate [80.0% (95% CI, 59.3–93.2)]. Median PFS was 12.0 months (95% CI, 7.3 to NA). The median DOR and OS were not reached. No new safety signal was observed in Chinese patients. The most common ≥ grade 3AE were white-cell count decreased (in 87.6% of the patients), neutropenia (in 82.9%), pyrexia (in 73.3%). Eighty-one patients experienced cytokine release syndrome (CRS) of any grade, and 16 (15.2%) patients occurred grade 3 or higher. Any grade of neurologic events (NE) occurred in 17 (16.2%) patients, and only 1 (1.0%) patients were grade 4. No grade 5 CRS or NE appeared (Figure 1B-C). Fifty-five percent received tocilizumab and 52% received glucocorticoids to manage CRS and/or NE. The median cumulative cortisone-equivalent corticosteroid dose was 2000 mg, which was similar to ZUMA-1 cohort6 and much smaller than ZUMA-1 cohort1+2. The research was funded by: The research was funded by Fosun Kite Biotechnology Co., Ltd., Shanghai, China. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies No conflicts of interests pertinent to the abstract.

Dose-Response Meta-Analysis of Corticosteroid Effects in SARS Outbreak: A Model for Risk Stratification and Screening Strategy for Osteonecrosis of Femoral Head Post-Corticosteroid Therapy for COVID-19.

Corticosteroids (CS) have been used in the management regimens for COVID-19 disease to mitigate the cytokine storm and ill effects of the pulmonary inflammatory cascade. With the rampant use of CS, clinicians started reporting the occurrence of osteonecrosis of the femoral head (OFH). In this systematic review, we aim to analyze the literature and identify the definitive cumulative dose and duration of CS needed for the development of OFH based on the SARS model and generate a risk-based screening recommendation for OFH in convalescent COVID-19 patients to facilitate early identification and management. An electronic database search was conducted until December 2022 in PubMed, Web of Science, Embase, and CNKI (China Knowledge Resource Integrated Database). Studies involving CS therapy and osteonecrosis data in SARS patients were included. Three authors independently extracted the data from the included studies and a dose-response meta-analysis was performed for various doses and duration of CS utilized in the included studies. We selected 12 articles with 1728 patients in the analysis. The mean age was 33.41 (±4.93) years. The mean dosage of CS administered was 4.64 (±4.7) g which was administered for a mean duration of 29.91 (±12.3) days. The risk of osteonecrosis increases at pooled OR of 1.16 (95% CI 1.09-1.23, p < 0.001) per 2.0 g increase in the cumulative dose of CS usage. Similarly, the risk increases at pooled OR of 1.02 (95% CI 1.01-1.03, p < 0.001) per 5 days of increase in the cumulative duration of CS usage. A cumulative dosage of 4 g and a duration of 15 days were determined as the critical cut-off for the non-linear dose-response relationship observed. Appropriate and frequent screening of these individuals at regular intervals would help in the identification of the disease at an early stage in order to treat them appropriately.

ATP-binding cassette G1 membrane transporter-mediated cholesterol efflux capacity influences coronary atherosclerosis and cardiovascular risk in Rheumatoid Arthritis

ObjectivesCholesterol efflux capacity (CEC) measures the ability of high-density lipoprotein (HDL) to remove cholesterol from macrophages and reduce the lipid content of atherosclerotic plaques. CEC inversely associated with cardiovascular risk beyond HDL-cholesterol levels. CEC through the ATP-binding-cassette G1 (ABCG1) membrane transporter is impaired in rheumatoid arthritis (RA). We evaluated associations of ABCG1-CEC with coronary atherosclerosis, plaque progression and cardiovascular risk in RA. MethodsCoronary atherosclerosis (noncalcified, partially, fully-calcified, low-attenuation plaque) was assessed with computed tomography angiography in 140 patients and reevaluated in 99 after 6.9 ± 0.3 years. Cardiovascular events including acute coronary syndromes, stroke, cardiovascular death, claudication, revascularization and hospitalized heart failure were recorded. ABCG1-CEC was measured in Chinese hamster ovary cells as percentage of effluxed over total intracellular cholesterol. ResultsABCG1-CEC inversely associated with extensive atherosclerosis (≥5 plaques) (adjusted odds ratio 0.50 [95% CI 0.28–0.88]), numbers of partially-calcified (rate ratio [RR] 0.71 [0.53–0.94]) and low-attenuation plaques (RR 0.63 [0.43–0.91] per standard deviation increment). Higher ABCG1-CEC predicted fewer new partially-calcified plaques in patients with lower baseline and time-averaged CRP and fewer new noncalcified and calcified plaques in those receiving higher mean prednisone dose. ABCG1-CEC inversely associated with events in patients with but not without noncalcified plaques, with <median but not higher CRP and in prednisone users but not nonusers (p-for-interaction = 0.021, 0.033 and 0.008 respectively). ConclusionABCG1-CEC inversely associated with plaque burden and vulnerability, and plaque progression conditionally on cumulative inflammation and corticosteroid dose. ABCG1-CEC inversely associated with events specifically in patients with noncalcified plaques, lower inflammation and in prednisone users.

Severe infections in patients with systemic lupus erythematosus from Tunisia: Prevalence and risk factors.

Since the improvement in management and the reduction of mortality caused by the disease activity, infections have represented the main cause of morbidity and mortality in systemic lupus erythematosus patients. We aimed to determine the prevalence and identify risk factors of severe infections in systemic lupus erythematosus patients. We conducted a retrospective study on 93 Tunisian lupus patients followed between 2010 and 2019. The mean age of the disease was 33.63 ± 13.76years. Fifty-two patients had 118 infections and 16% of the infections were serious. The bivariate analysis revealed a positive correlation between the total cumulative doses of corticosteroids and the number of serious infections (p = 0.009). The multivariate study has shown that the number of flares (p = 0.03), pulmonary manifestations (p = 0.01), pleuritis (p = 0.001), and the total cumulative dose of corticosteroids (p = 0.04) were independent risk factors of severe infections (p < 0.001). The use of antimalarials exerted a protective effect from severe infection [OR = 0.19 (95% CI 0.03-0.9)] p < 0.03.

Postnatal corticosteroids and developmental outcomes in extremely preterm or extremely low birth weight infants: The Victorian Infant Collaborative Study 2016-17 cohort.

Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.

Comparison of Cumulative Corticosteroid Doses in Critically-ill COVID-19 Patients

Comparison of Cumulative Corticosteroid Doses in Critically-ill COVID-19 Patients

Secondary infections in critically ill patients with COVID-19: A retrospective single-center study.

Patients infected with COVID-19 admitted to the intensive care unit (ICU) may have a higher incidence of developing secondary infections. These infections can further deteriorate the hospital course and increase mortality. Therefore, the objectives of this study were to investigate the incidence, associated risk factors, outcomes, and pathogens associated with secondary bacterial infections in critically ill patients with COVID-19. All adult COVID-19 patients admitted to the intensive care unit requiring mechanical ventilation from October 1, 2020 until December 31, 2021 were screened for inclusion in the study. A total of 86 patients were screened and 65 who met the inclusion criteria were prospectively entered into a customized electronic database. The database was then retrospectively analyzed to investigate secondary bacterial infections. Of the 65 patients included, 41.54% acquired at least one of the studied secondary bacterial infections during the course of their ICU stay. The most common secondary infection (59.26%) seen was hospital-acquired pneumonia followed by acquired bacteremia of unknown origin (25.92%) and catheter-related sepsis (14.81%). Diabetes mellitus (P = <.001), cumulative dose of corticosteroids (P = 0.001), were associated with an increased risk of secondary bacterial infection. The most commonly isolated pathogen in patients with secondary pneumonia was Acinetobacter baumannii. Staphylococcus aureus was the most common organism associated with a bloodstream infection and catheter-related sepsis. The incidence of secondary bacterial infections was high in critically ill patients with COVID-19 and was associated with a longer duration of admission to the hospital and ICU and a higher mortality. Diabetes mellitus and cumulative dose of corticosteroids were associated with significantly increased risk of secondary bacterial infection.

Böbrek Nakli Alıcılarında Düşme: Geleneksel Derleme

Kidney transplantation is the gold standard treatment for end stage renal disease. Despite the improvement in survival and quality of life, the prevalence of falls is higher in kidney transplant recipients. Factors that increase the risk for falls include female gender, older age, impaired balance control, lower ankle dorsiflexion muscle strength, high serum creatinine levels, and the use of antidiabetic medications. Functional limitations, fatigue, low cardio-respiratory fitness, changes in mineral metabolism lead to bone mineral disease in chronic kidney disease and can finally play an important role in occurrence of accidental falls in pre-transplantation period. Fractures without dislocations or head injury-related hemorrhages constitute a majority for the serious fall-related injury types. In addition to many factors such as cumulative dose of corticosteroids, younger age at transplantation, hyperparathyroidism, vitamin D deficiency and renal osteodystrophy, risk of falls also contribute to increased post-transplantation bone loss and fracture risk. Hip fractures requiring hospitalization in the post-kidney transplant period are associated with a higher risk of mortality. It is important to understand the underlying mechanisms for falls in kidney transplant recipients in order to prevent severe injuries including fractures and decrease healthcare costs. The awareness of healthcare professionals should be increased for falls in this specific population to design multidisciplinary therapeutic approaches including risk factor assessment, exercise programs and patient and caregiver education not only for kidney transplant recipients but also for the patients waiting on a transplantation list.

Development of a web tool to calculate the cumulative dose of glucocorticoids

IntroductionGlucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. ObjectiveThe aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. MethodsThe total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. ResultsA simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. ConclusionThis tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.

Efficacy of corticosteroids as an adjunctive therapy in the treatment of community-acquired pneumonia: a systematic review and meta-analysis

The objective of this study was to systematically evaluate the clinical efficacy of the complementary use of corticosteroids in the treatment of community-acquired pneumonia (CAP). We searched all relevant documents in five scientific databases from inception to June 2022 to collect clinical trials (randomized controlled trials and controlled trials) reporting on the adjunctive use of corticosteroids in CAP treatment. The primary outcome was mortality, and secondary outcomes included the time to clinical stability, therapeutic efficacy, duration of antibiotic treatment and length of hospital/ICU stay. Therapeutic efficacy was defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough. Clinical stability was defined by improvements in laboratory values. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the quality of literature. Statistical analysis and meta-analysis of intervention measures and indicators were performed with IBM SPSS and RevMan 5.4 software. Nine randomized controlled trials comprising 2673 participants with CAP (1335 in the corticosteroid group and 1338 in the control group) were identified and included in this study. The mean cumulative corticosteroid dose and treatment duration were 298.00±287.140 mg and 5.22±1.787 days, respectively. Corticosteroid treatment was not associated with a significant decrease in mortality (RR; 95% CI, 0.96 [0.67–1.38], P=0.83). Because of the low number of included patients in our study, more studies with larger sample sizes and high-quality randomized, double-blind controlled trials are needed to confirm the results.

070 Treating Bullous Pemphigoid by Inhibiting FcRn: A Phase 2/3 Trial with Efgartigimod

Efgartigimod (EFG) is an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor (FcRn), thereby reducing the levels of circulating immunoglobulin G (IgG), including pathogenic IgG autoantibody, levels. EFG is clinically efficacious and generally well tolerated in phase 2 and 3 trials in multiple IgG-mediated disorders. Bullous pemphigoid (BP) is an autoimmune blistering disease, characterized by subepidermal blisters and mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230, structural proteins of the dermal-epidermal junction. Administration of an EFG analogue prior to and after that of pathogenic anti-BP180 IgG antibodies in a BP mouse model demonstrated efficacy in reducing skin disease activity. EFG will be evaluated as a therapy for BP in BALLAD, a phase 2/3 randomized, double-blinded, placebo-controlled trial (NCT05267600). BALLAD will be conducted in two parts – a proof-of-concept Part A (N=40) and a confirmatory Part B (N=120). Both parts are identical in schedule, structure, assessments, and conduct. 2000 mg EFG PH20 SC will be given on days 1 and 8, and 1000 mg EFG PH20 SC will be given weekly through week 35. Oral corticosteroids starting at 0.5 mg/kg/day of prednisone will be administered to the EFG PH20 SC and placebo PH20 SC groups and adjusted to each participant’s disease status. The primary endpoint is the proportion of participants in complete remission on minimal oral corticosteroid therapy (≤0.1 mg/kg/day) for ≥8 weeks at week 26. Key secondary endpoints include cumulative dose of oral corticosteroids from day 1 to week 36, change in the Bullous Pemphigoid Disease Area Index (BPDAI) score, incidence and severity of adverse events, and quality of life scores.

Corticosteroid administration and glycemic outcomes during treatment of acute exacerbation of chronic obstructive pulmonary disease

BackgroundWhile international guidelines recommend low doses of systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) clinical practice patterns show significant heterogeneity. Increasing doses of corticosteroids have inconsistently been associated with a greater risk of hyperglycemia. MethodsPatients admitted to inpatient services for AECOPD were retrospectively enrolled. Hospitalization corticosteroid doses, daily blood glucose levels, and other markers of corticosteroid excess were collected. Correlative and regression analyses were conducted to assess the relationship between corticosteroid dose and average hospitalization blood glucose. ResultsDaily corticosteroid dose significantly predicted a higher blood glucose (rs=0.179, p=0.0095; p<0.0028 respectively) and cumulative corticosteroid dose predicted a longer hospital length of stay in bivariate and multivariate analyses (rs=0.679, p<0.0001; p<0.0001 respectively). Patients that experienced hypernatremia, hypokalemia, acute hyperglycemia, and acute hypertension received larger corticosteroid doses than patients that did not experience these complicating events. ConclusionsWe identified that increasing amounts of corticosteroids administered to inpatients experiencing AECOPD experienced higher average hospitalization blood glucose values, protracted hospitalizations, and other untoward effects.

The relationship between cumulative dose of immunosuppressive agents and COVID-19-associated mucormycosis: A multicenter cross-sectional study.

Immunosuppressive therapy has a key role in developing coronavirus disease-2019 (COVID-19)-associated mucormycosis. In this study, we investigated the effect of the type and cumulative dose of immunosuppressive agents on COVID-19-associated mucormycosis. We designed a descriptive cross-sectional study involving three COVID-19 hospitals in Iran. Clinical and demographic data were gathered from the medical records and checked by two independent researchers to minimize errors in data collection. Seventy-three patients were included in the study. The mean age of cases was 57.41 (SD = 12.64) and 43.8% were female. Among patients, 20.5% were admitted to the intensive care unit (ICU) during COVID-19. Furthermore, 17 patients (23.29%) had a history of diabetes mellitus. Sixty-nine patients (94.52%) had a history of receiving corticosteroids (dexamethasone) during treatment of COVID-19, and of those, five patients (6.85%) received Tocilizumab beside. The mean cumulative dose of corticosteroids prescribed was 185.22 mg (SD = 114.738). The average cumulative dosage of tocilizumab was 720 mg (SD = 178.89). All of the included patients received amphotericin B for mucormycosis treatment, and 42 survived (57.53%). Also, there was a significant relationship between hospitalization in ICU for COVID-19 and the mucormycosis outcome (p = 0.007). However, there weren't any significant associations between cumulative doses of immunosuppressive drugs and mucormycosis outcome (p = 0.52). The prevalence of COVID-19-associated mucormycosis is increasing and should be considered in the treatment protocols of COVID-19. Controlling risk factors such as diabetes, malignancy and the administration of immunosuppressive agents based on recommended dosage in validated guidelines are ways to prevent mucormycosis.

Isolated polymyalgia rheumatica: a cross-sectional, single-center, retrospective cohort study

Aim: The aim of the study was to review sociodemographic variables, clinical and laboratory findings, disease progression and treatment response of patients with isolated polymyalgia rheumatica and to investigate the effect of initial steroid dose and maintenance treatment on the progression of clinical and laboratory outcome. &#x0D; Material and Method: The medical records of 39 polymyalgia rheumatic patients who followed up between 2001 and 2020 were screened. After excluding patients with overlapped giant cell arteritis and malignancies, 19 polymyalgia rheumatica patients (female:16 and male:3) were included in the study. Demographic data, anthropometric measurements, comorbidities, initial symptom, physical examination, clinical and laboratory (acute phase reactants) findings, medications, changes in treatment status, and cumulative steroid dose were recorded. The medical data of first (1st month), second (4th month), and third (7th month) visits were noted according to the structured form. &#x0D; Results: The mean age was 68±8 years and the mean initial steroid dose was 21.5±8.9 mg. While the complaints regarding polymyalgia rheumatica decreased in 52.6% of patients (n=10) in the first visit, those complaints regressed in 47.4% (n=9) and 73.7% (n=14) of patients in the second and third visit, respectively. In the first visit (1st month), the mean erythrocyte sedimentation rate and C-reactive protein values were 21.7±12.3 mm/h and 5.8±5.1 mg/dl. In the second (4th month) and third visits (7th month), while the mean erythrocyte sedimentation rate was found as 36.5±27.3 mm/h and 27.3±18.6 mm/h, the mean C-reactive protein was 27.2±43.0 mg/dl and 17.6±30.2 mg/dl, respectively. Clinical remission was observed in 47.4% of patients (n=9) in the second visit and in 31.6% of patients (n=6) in the third visit. Median cumulative corticosteroid doses were 600 mg in first visit, 960 mg in second visit, and 1346 mg in the third visit. &#x0D; Conclusion: The clinical characteristics and the initial steroid dose were compatible with the literature. Even though cumulative corticosteroid doses were quite high, lower remission rates were observed in these patients. The possible reason for this was considered to be the non-adherence of the patients to the treatment.

Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis.

Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population. Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima-media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed. Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P < 0.001 for both). Moreover, within the EGPA cohort, CCA-IMT tended to increase with disease duration (P = 0.034) and corticosteroid cumulative dose (P = 0.004). No significant associations were found between CCA-IMT, ANCA status, other clinical features and therapeutic regimens. Notably, the prevalence of traditional cardiovascular risk factors was comparable in patients with vs without an increased CCA-IMT. Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.

Predisposing Factors of Tuberculosis Infection in Systemic Lupus Erythematosus Patients: A Single-Center Case-Control Study.

Introduction: Indonesia has the second-highest tuberculosis cases in the world, according to the global WHO tuberculosis report, amounting to approximately 10% of the world's tuberculosis cases. Systemic lupus erythematosus (SLE) patients are at an increased risk for tuberculosis infection. This research aims to analyze the association between corticosteroid pulse dose, corticosteroid cumulative dose, SLE disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and lupus nephritis status with the development of tuberculosis in SLE patients.Methods: This research was a matched case-control study to identify risk factors of tuberculosis infection in SLE patients. Data were taken from medical records of Cipto Mangunkusumo National General Hospital, a national tertiary hospital. Inclusion criteria were patients who meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria of SLE in the period of 2012-2016 or patients who meet the SLICC 2012 SLE criteria and developed tuberculosis between 2012 and 2016. Statistical analyses used were bivariate analysis and correlation analysis. All statistical analyses were conducted using SPSS software (IBM Corp., Armonk, NY). All statistical analyses were defined as statistically significant when the p-value was less than 0.05.Results: A total of 48 SLE patients were included from medical records consisting of 24 SLE patients with tuberculosis infection and controls of 24 SLE patients without tuberculosis infection. In this study, it was observed that the presence of lupus nephritis (p = 0.001), administration of pulse corticosteroids (p = 0.048), high corticosteroid cumulative dose (p = 0.001), and high SLEDAI score (p = 0.003) were associated with tuberculosis infection. Correlation analysis showed that all of these variables had a weak positive correlation with tuberculosis infection in SLE patients.Conclusion: SLE patients with lupus nephritis, administration of pulse corticosteroids, high cumulative corticosteroid dose, and high SLEDAI score have a higher risk of tuberculosis infection. Clinicians and patients should be aware of these risk factors in SLE patients to prevent tuberculosis infection. Corticosteroid pulse dose should be avoided in SLE patients and if it is needed, tuberculosis prophylaxis may be considered.

P888: REPLACING STEROIDS IN TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA: THE PHASE 2 ISATUXIMAB-BORTEZOMIB-LENALIDOMIDE-DEXAMETHASONE REST STUDY

Background: Standard therapies for newly diagnosed multiple myeloma (NDMM) patient’s ineligible for autologous stem-cell transplantation (ASCT) have been lenalidomide-dexamethasone (Rd), bortezomib-lenalidomide-dexamethasone (VRd) or bortezomib-melphalan-prednisone (VMP). The benefit of adding an anti-CD 38 monoclonal antibody (mAb) to the standard treatments of VMP and Rd has been demonstrated in two large phase 3 studies (Facon, 2019. Mateos, 2018). Isatuximab is an anti-CD38 mAb approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone to treat relapsed/refractory MM, and has also shown clinical responses as combination therapy to treat NDMM (Trudel, 2019). Corticosteroids have been the backbone of most myeloma targeted therapies since the discovery of their effectiveness. Due to the continuous treatment paradigm, the cumulative dose of corticosteroids in patients is substantial. Steroids inflict reduction in both short- and long-term quality of life and increase patients’ receptiveness for infections. Infections are one of the main reasons for complications and death during active first line treatment, and the rate rises with age. Both steroid-free regimens and regimens with reduced corticosteroids have demonstrated improved safety and similar efficacy as regimens containing steroids. Aims: The study will evaluate isatuximab (Isa) in combination with bortezomib (V) and lenalidomide (R) with minimal dexamethasone (d) as first-line treatment in transplant-ineligible patients. The primary endpoint is the number of patients who achieve measurable residual disease negative (Euroflow NGF 10-5) complete response during and/or after 18 cycles of study treatment. Secondary endpoints include progression free survival, overall survival, overall response rate (ORR), safety evaluations and patient-reported outcome. Methods: The REST study is an academic, single arm, open-label, phase 2 study of NDMM patients ineligible for ASCT. 50 patients will be included and receive Isa-VRd (Isa:10 mg/kg IV Days 1, 8, 15, 22 during cycle 1, QW cycle 2-18; V: 1,3 mg/m2 SC Days 1,8,15 during cycle 1-8; R: 25 mg PO Days 1-21 during all cycles; d: 20 mg PO Days 1,8,15,22 only for the first 2 cycles), all 28-day cycles. Results: As of January 31, 2022, 17 patients have been enrolled. Baseline characteristics can be found in Table 1. At data-cutoff, the median number of cycles started by patients was 3.6 (range 1-8) and the median duration of exposure was 16 (range 3-28) weeks. 8 patients developed 14 grade ≥3 non-hematological adverse eventd (AE), including infections (n=7), fever (n=1), skeletal pain (n=2), acute renal failure (n=1), peripheral sensory neuropathy (n=1), diarrhea (n=1) edema (n=1). There were no AEs leading to definitive treatment discontinuation. At a follow up of 6 months, the ORR was 100% (15/15) and the ≥very good partial response rate was 53.3% (8/15 patients). Image:Summary/Conclusion: Isa-VRd in the transplant ineligible population has a tolerable safety profile. Isa-VRd is showing encouraging preliminary efficacy in NDMM ineligible for transplant. Enrollment and follow-up is ongoing. Acknowledgements: Sanofi sponsors the REST study.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. A retrospective, observational study. Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Effects of cumulative doses of corticosteroids on the recovery of patients with COVID-19

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)