High-dose Corticosteroid Use Research Articles

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A Nationwide Nested Case-Control Study

BackgroundAlthough it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. MethodsA nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. ResultsCompared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. ConclusionsThe ONFH risk increased rapidly when cumulative prednisolone use was ≥1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

Effect of Corticosteroids on Long-Term Humoral and Memory T-Cell Responses in Follow-Up Visit of Hospitalized Patients With COVID-19

Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain, as it relates to the extent of immediate, antigen-specific defense provided by protective memory. What is the effect of corticosteroids on long-term humoral and T-cell immune responses? In this retrospective cohort study conducted at a single center, we analyzed data from a cohort who had survived COVID-19 to compare the 1-year seropositivity and titer changes in neutralizing antibodies (NAbs) and SARS-CoV-2-specific antibodies. Additionally, we evaluated the magnitude and rate of SARS-CoV-2-specific T-cell response in individuals who received corticosteroids during hospitalization and those who did not. Our findings indicated that corticosteroids do not statistically influence the kinetics or seropositive rate of NAbs against the Wuhan strain of SARS-CoV-2 from 6months to 1 year. However, subgroup analysis revealed a numerical increase of NAbs titers, from 20.0 to 28.2, in categories where long-term (> 15days) and high-dose (> 560mg) corticosteroids were administered. Similarly, corticosteroids showed no significant effect on nucleoprotein and receptor-binding domain IgG at 1 year, except for spike protein IgG (β, 0.08; 95%CI, 0.04-0.12), which demonstrated a delayed decline of titers. Regarding T-cell immunity, corticosteroids did not affect the rate or magnitude of T-cell responses significantly. However, functional assessment of memory Tcells revealed higher interferon-γ responses in CD4 (β, 0.61; 95%CI, 0.10-1.12) and CD8 (β, 0.63; 95%CI, 0.11-1.15) memory Tcells in the corticosteroids group at 1 year. Based on our findings, short-term and low-dose corticosteroid therapy during hospitalization does not appear to have a significant effect on long-term humoral kinetics or the magnitude and rate of memory T-cell responses to SARS-CoV-2 antigens. However, the potential harmful effects of long-term and high-dose corticosteroid use on memory immune responses require further investigation.

High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide Population-Based Matched Cohort Study.

Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain. We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA). During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25-1.76) and 90 days (aHR, 1.63; CI, 1.44-1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79-1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94-9.43). Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B cell lymphoma, follicular lymphoma with histologic transformation to large B cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

Orthopedic Consequences of Post-COVID-19 High-dose Corticosteroid Use and Vaccination: An Update Study

Orthopedic Consequences of Post-COVID-19 High-dose Corticosteroid Use and Vaccination: An Update Study

Complications of Corticosteroid Therapy: A Comprehensive Literature Review.

Relevance to Patient Care and Clinical Practice: Corticosteroids are among the most prescribed medications, particularly during the COVID-19 era. The literature has clearly highlighted the dangers of prolonged, high-dose corticosteroid use, which is important for clinicians to consider before treating patients in their clinical practices. Objective: The objective of this article is to review the literature on complications of corticosteroid use, review corticosteroid pharmacokinetics, and provide an updated reference on risks associated with corticosteroid therapy, especially at higher doses. Data Sources: A conventional literature search of PubMed was conducted without restrictions on publication date. Search terms included "corticosteroids," "avascular necrosis," "gastrointestinal bleeding," and "complications." Study Selection and Data Extraction: Pertinent systematic review/meta-analyses and randomized controlled trials were reviewed for study inclusion. Data Synthesis: Corticosteroids were associated with complications including avascular necrosis, gastrointestinal bleeding, myocardial infarction, heart failure, cerebrovascular events, diabetes mellitus, psychiatric syndromes, ophthalmic complications, tuberculosis reactivation, and bacterial sepsis. Increased daily and cumulative doses were associated with increased excess risk of complications. Cumulative doses greater than 430 mg prednisone equivalent were shown to increase the excess risk of avascular necrosis, with progressively higher rates with higher doses. Risk of gastrointestinal bleeding was significantly increased with corticosteroid usage in the in-patient but not out-patient setting. Conclusion: Since corticosteroids have been associated with the aforementioned severe complications and frequent medicolegal malpractice claims, counseling and informed consent should be performed when prescribing moderate-high dosages of corticosteroids. Further research is needed to characterize the long-term effects of corticosteroid usage in COVID-19 patients.

Mucormycosis—The Rising Epidemic in a Pandemic: An Observational Case Study in a Tertiary Care Hospital

Mucormycosis is a rare and ominous fungal disease caused by the order Mucorales fungi. As per Indian data, uncontrolled diabetes is the main risk factor associated with mucormycosis. But during this SARS COV-2 pandemic, a huge rise in the number of mucormycosis cases has been observed in different states in India in last 10-12 months in the second wave. The immune dysfunction caused by this virus and the use of high doses of steroids appears to be a double-edged sword and causes immunosuppression with hyperglycemia, increasing the risk of secondary bacterial and invasive fungal infections (IFIs). Objective We conducted a prospective observational study involving individuals with proven mucormycosis in ABVIMS &amp; Dr RML Hospital, New Delhi. The demographic profile with various clinical presentations, histopathological findings, predisposing factors, management, and final outcomes were recorded. Results We included 53 patients in our study. Rhino-orbital-cerebral mucormycosis was the most common (21/53, 39.6%) presentation followed by rhino-orbital (17/53, 32.0%), rhino-cerebral (10/53, 18.8% ) rhinosinusitis (4/53, 7.5%) and pulmonary involvement in 1/53, (1.8%). The cutaneous involvement was seen in 8 patients (15.0%), disseminated mucormycosis as meningitis in 2 patients (3.7%), and dual fungal infection with aspergillosis was seen in 2 patients (3.7%). The predisposing factors being diabetes mellitus (40/53, 75.4%), with newly diagnosed diabetes in previously undiagnosed (10/ 53, 18.8%), SARS-COV-2 (33/53, 62.2%), steroid intake (30/53, 56.6% ), prolonged hospital stay (29/53, 54.7%), use of oxygen therapy (19/53, 35.8%), and diabetic ketoacidosis in 2 patients (3.7%) Amphotericin B (liposomal form) was the primary therapy in all 53 patients. Hypokalemia (8/53, 15.0%) was seen as side effect of amphotericin-B although renal functions were normal in all patients. Surgical debridement was performed in 43(77.3%) patients and transcutaneous retrobulbar amphotericin-B (TRAMB) was given in 16 patients (30.1%). Total mortality in our study is of 9 patients (16.9%). Conclusions Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis which also includes newly diagnosed diabetes. Hyperglycemia and immune dysregulation by SARS-CoV-2 and high dose corticosteroid use on large scale served a favorable environment for this invasive fungus.

Risk factors and clinical impact of COVID-19-associated pulmonary aspergillosis: Multicenter retrospective cohort study.

Background/AimsThe risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes.MethodsBetween January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use.ResultsA total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091).ConclusionsCAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Outcomes of COVID-19 in a cohort of pediatric patients with rheumatic diseases

BackgroundThere are few reports of COVID-19 in pediatric patients with rheumatic diseases. This study describes the clinical presentation and outcomes of COVID-19 in this population.MethodsWe analyzed a single-center case series of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Demographic, baseline and COVID-19 associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis.ResultsFifty-five cases were identified: 45 (81.8%) in the ambulatory group and 10 (18.2%) hospitalized. African American race (OR 7.78; 95% CI [1.46–55.38]; p = 0.006) and cardiovascular disease (OR 19.40; 95% CI 2.45–254.14; p = 0.001) predominated in hospitalized patients. Active rheumatic disease (OR 11.83; 95% CI 1.43–558.37; p = 0.01), medium/high-dose corticosteroid use (OR 14.12; 95% CI [2.31–106.04]; p = 0.001), mycophenolate use (OR 8.84; 95% CI [1.64–63.88]; p = 0.004), rituximab use (OR 19.40; 95% CI [2.45–254.14]; p = 0.001) and severe immunosuppression (OR 34.80; 95% CI [3.94–1704.26]; p = < 0.001) were associated with increased odds of hospitalization. Fever (OR 7.78; 95% CI [1.46–55.38]; p = 0.006), dyspnea (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003), chest pain (OR 13.20; 95% CI [1.53–175.79]; p = 0.007), and rash (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003) were more commonly observed in hospitalized patients. Rheumatic disease flares were almost exclusive to hospitalized patients (OR 55.95; 95% CI [5.16–3023.74]; p < 0.001).. One patient did not survive.ConclusionsMedium/high-dose corticosteroid, mycophenolate and rituximab use, and severe immunosuppression were risk factors for hospitalization. Fever, dyspnea, chest pain, and rash were high-risk symptoms for hospitalization. Rheumatic disease activity and flare could contribute to the need for hospitalization.

PND70 Procedure Coding Versus Pharmacy-Dispensing Claims for Assessing Steroid Use in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Primary Immunodeficiency Diseases (PIDD)

Accounting for high-dose systemic corticosteroid (SCS) use is critical for unbiased real-world studies of patients with inflammatory or immunological disorders. SCS administration may be recorded as procedural codes for injections/infusions (Healthcare Common Procedural Coding System; HCPCS) or pharmacy-dispensed medications (National Drug Code; NDC). Understanding the patterns of SCS coding is important for the valid design of real-world studies. US patients initiating immunoglobulin (IG) treatment for CIDP or PIDD were identified in IBM MarketScan Research Databases from 2008–2018 and 2012–2018, respectively; high-dose SCS use was determined. Patients identified by each coding system were compared. Among 3975 patients with CIDP and initiating IG, 1382 (34.8%) had prior high-dose SCS use, identified by HCPCS in 925 (23.3%) patients and NDC in 646 (16.3%) patients (non-mutually exclusive). Compared with NDC-identified patients, HCPCS-identified patients were older, more likely to be male, from Southern US, receiving outpatient IG, and have had back pain, central nervous system disorders, diabetes, dyslipidemia, hypertension, and osteoarthritis. HCPCS-identified patients were less likely to have deep vein thrombosis (DVT), opioid use, or prior use of immunomodulating agents. Among 17,931 PIDD patients initiating IG, 11,576 (64.6%) had prior high-dose SCS use, identified by HCPCS in 8826 (49.2%) patients and NDC in 6342 (35.4%) patients (non-mutually exclusive). Compared with NDC-identified patients, HCPCS-identified patients were older, more likely to be female, from Southern US, receiving outpatient IG, using Medicare, and more often had low Risk Vital Sign scores (disease severity algorithm) and have had cancer, fibromyalgia, inflammatory bowel disease, and obesity. HCPCS-identified patients were less likely to have had pneumonia or DVT. HCPCS and NDC identification of high-dose SCS use may elucidate differences in patient populations, which should be considered in real-world studies.

PBI19 Replicating Clinical Trial Exclusion Criteria in a Claims-Based Cohort of Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) Initiating Intravenous Immunoglobulin (IVIG) Treatment

CIDP is a debilitating, progressive, or relapsing disorder, affecting the peripheral nervous system, for which immunomodulatory IVIG is considered a first-line treatment. We replicated the exclusion criteria from a randomized controlled trial (RCT) in a real-world, claims-based cohort in this population to evaluate how a real-world population differs from RCT populations. Patients initiating IVIG after diagnosis with CIDP were identified from commercial, Medicare, and Medicaid claims, from 2008 through 2018, at their first use of IVIG following 6 months without use of immunoglobulins. Comorbidity- and treatment-based exclusion criteria from an ongoing RCT (NCT02549170) in CIDP patients were defined in claims data and applied to the IVIG cohort (using 6–12 months of available patient data prior to enrollment) to observe the impact on the study population. Not all RCT exclusion criteria could be defined in the claims data; those that could be defined included other neuropathies, multiple sclerosis, Parkinson’s disease, diabetic neuropathy, high-dose systemic corticosteroid use, plasma exchange/plasmapheresis, and immunosuppressant use. Of the 3975 IVIG initiators with CIDP identified, 75.4% would have met the RCT exclusion criterion of diagnosis of a different neuropathy, 26.5% had corticosteroid use in the 90 days prior to eligibility, and 15.9% had diabetic neuropathy or uncontrolled diabetes. Other RCT exclusion criteria were each present in <7.0% of the study population. After cumulatively applying all RCT exclusion criteria, 86.1% of the original study population was excluded. Applying exclusion criteria used in an RCT would have excluded most of the identified IVIG users with CIDP, primarily resulting from one criterion: other neuropathy. Although some RCT exclusions may be necessary to reduce misclassification of CIDP status, the resulting RCT-replicated population does not accurately reflect real-world users of IVIG.

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

Chronic Pulmonary Aspergillosis Following Nontuberculous Mycobacterial Infections: An Emerging Disease.

Chronic pulmonary aspergillosis (CPA) following nontuberculous mycobacterial (NTM) lung disease is being increasingly recognized, especially in countries where tuberculosis is not endemic, with an incidence rate of 3.9–16.7%. NTM lung disease has been identified as a predictor of mortality in CPA patients. The major risk factors for NTM-associated CPA include fibrocavitary NTM lung disease, the presence of pulmonary emphysema, and high-dose corticosteroid use. The onset of CPA is 1.5–7 years following the diagnosis of NTM lung disease. The diagnosis can be made using standard criteria; however, serological diagnosis using Aspergillus precipitin has demonstrated a higher sensitivity and specificity when compared with fungal culture from respiratory specimens. Treatment is challenging since rifampicin and oral triazoles should not be used concomitantly. The prognosis is poor, and the factors associated with worse prognosis are corticosteroid use and high C-reactive protein level.

Delayed hospital admission and high-dose corticosteroids potentially prolong SARS-CoV-2 RNA detection duration of patients with COVID-19.

Coronavirus disease 2019 (COVID-19) with the infection of SARS-CoV-2 has become a serious pandemic worldwide. However, only few studies focused on risk factors of prolonged SARS-CoV-2 RNA detection among patients with COVID-19. We included 206 adult patients with laboratory-confirmed COVID-19 from two hospitals between 23 Jan and 1 April 2020. Least absolute shrinkage and selection operator (LASSO) analysis was used to screen out independent risk factors of SARS-CoV-2 RNA detection. By multivariate binomial logistic regression analysis and Cox regression analysis, we further determined the associations between SARS-CoV-2 RNA detection and potential risk factors. All patients had two negative SARS-CoV-2 tests with 33 days of median duration of SARS-CoV-2 RNA detection (interquartile range: 25.2–39 days). LASSO and binomial logistic regression analyses suggested that delayed hospital admission (adjusted OR = 3.70, 95% CI: 1.82–7.50), hypokalemia, and subpleural lesion (adjusted OR = 4.32, 95% CI: 1.10–16.97) were associated with prolonged SARS-CoV-2 RNA detection. By LASSO and multivariate Cox regression analyses, we observed that delayed hospital admission, subpleural lesion, and high-dose corticosteroid use were independent risk factors of prolonged SARS-CoV-2 RNA detection. Early hospital admission shortened 5.73 days of mean duration of SARS-CoV-2 RNA detection than delayed hospital admission after adjusting confounding factors. Our study demonstrated that delayed hospital admission and subpleural lesion were associated with prolonged SARS-CoV-2 RNA detection among patients with COVID-19. The use of high-dose corticosteroids should be interpreted with extreme caution in treating COVID-19.

Safety of Immunotherapy Rechallenge After Immune-related Adverse Events in Patients With Advanced Cancer.

This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P<0.001). The same subsequent irAEs recurrences occurred on 42% of RG, 4% of TCG, and 15% of NRG (P<0.001). On the RG, there was a nonstatistical trend of shortening interval time between time from treatment rechallenge to subsequent irAEs when compared with time from first treatment to initial grade≥2 irAEs (5.86 vs. 8.86 wk, P=0.114). Patients who had cardiac irAEs were not rechallenged. Several high-risk features were identified to prognosticate risk of irAEs recurrences upon treatment rechallenge, including age 65 years and above (P=0.007), programmed cell death protein 1 inhibitors (P<0.001), grade 3 irAEs (P=0.003), pneumonitis type (P=0.048), any systemic corticosteroid use (P=0.001)/high-dose systemic corticosteroid use (P=0.007)/prolonged ≥4-week corticosteroid use (P=0.001) for irAEs management, and early development of irAEs (P=0.003). Our study concluded that it was relatively safe to continue or rechallenge patients with advanced cancers on immunotherapy-based regimens postdevelopment of certain grade≥2 irAEs, except for cardiac, neurological, or any grade 4 irAEs. Subsequent irAEs were common, no more severe, involved the same organ sites, and occurred more quickly than the original irAE. Close monitoring of all potential irAEs is required when rechallenging a patient on immunotherapy, especially for patients with high-risk features.

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

BackgroundIn December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited.ObjectiveWe sought to evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19.MethodsPatients with COVID-19 admitted to Tongji Hospital from January 26, 2020, to February 5, 2020, were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients.ResultsWe identified 269 (49.1%) of 548 patients as severe cases on admission. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-α), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19.ConclusionsPatients with older age, hypertension, and high lactate dehydrogenase level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have a high risk of death.

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Healthcare resource utilization and costs associated with long-term corticosteroid exposure in patients with systemic lupus erythematosus

Objective To evaluate the association between exposure to oral corticosteroids and future healthcare resource utilization and costs for patients with systemic lupus erythematosus. Methods Adults diagnosed with systemic lupus erythematosus (index date) between 1 January 2008 and 30 June 2013 and naive to oral corticosteroids with continuous health plan enrollment for ≥6 months pre- and ≥5 years post-index were identified from a large health plan claims database. Per-patient monthly average daily dose of oral corticosteroids (prednisone or its equivalent) was calculated for the first 2 years post-index to categorize patients into four steroid exposure cohorts: low (≤5 mg/day), medium (6-20 mg/day), high (>20 mg/day) and no steroids. Differences in healthcare resource utilization and total healthcare costs during the third year post-index across corticosteroid exposure cohorts were modeled with adjustment for baseline characteristics. Results The study included 18,618 systemic lupus erythematosus patients (163 high dose, 1127 medium dose, 6717 low dose and 10,611 no steroids). Compared to low-dose corticosteroid users, high-dose corticosteroid users were more likely to have emergency room visits (39.3% vs. 29.7%; p = 0.0085) and to be hospitalized (21.5% vs. 12.3%; p = 0.0005). After adjustment for baseline characteristics, they also had significantly greater average annual total healthcare costs (US$60,366 vs. US$18,777; p < 0.0001). A 1 mg increase in corticosteroid average daily dose was associated with 1.07 times the average annual costs after adjusting for baseline characteristics ( p < 0.0001). Conclusion Long-term high-dose oral corticosteroid use was associated with significantly greater future healthcare resource utilization and costs. Judicious reduction in daily steroid dose may decrease the imminent economic burden associated with high-dose steroid use in systemic lupus erythematosus.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Past Time for Doctors to Lessen their Dependence on Corticosteroids in the Treatment of IBD.

Corticosteroids and antibodies to tumor necrosis factor (anti-TNF) are mainstays of treatment of acutely active IBD and while anti-TNF therapy is indicated for maintenance therapy, chronic corticosteroid therapy is associated with known significant risks. Nonetheless, chronic or recurrent corticosteroid treatment in IBD is common. In this edition of the journal Lewis et al. use Medicaid and Medicare databases to contrast adverse outcomes in persons with IBD and either corticosteroid or anti-TNF use. Compared to high dose corticosteroid use, anti TNF therapy is associated with less risk for death in Crohn's disease but no statistical difference in death outcomes in ulcerative colitis. The adverse effects of corticosteroids are well known yet vigilance is still required to ensure their use is limited to the short term.