Use Of Tocilizumab Research Articles

SEVERE HYPERTRIGLYCERIDEMIA DUE TO TOCILIZUMAB IN COVID-19 TREATMENT: A CASE REPORT

Introduction and aim: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has been extensively studied in recent years. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, is recently used for the treatment of severe chronic inflammation in patients with COVID-19. However, there is a paucity of information on the side effects associated with the use of tocilizumab in patients with COVID-19. Thus, we aim is to present a case of a patient with complications after COVID-19 infection who received treatment with tocilizumab.
 Case description: We present the case of a young, Caucasian, male patient with severe hypertriglyceridemia, acute pancreatitis, and diabetes mellitus after tocilizumab treatment for COVID-19. This study was descriptive and observational, and its data were collected through detailed anamnesis and evaluation of laboratory and imaging tests performed after COVID-19 infection and hospitalization for the treatment of acute pancreatitis.
 Conclusion: This case is a reminder that a broader understanding of this drug is imperative for healthcare providers to be able to identify and treat its side effects as early as possible.

P-007 Prognostic impact of corticosteroid and tocilizumab use on the efficacy of chimeric antigen receptor T-cell therapy for relapsed/ refractory multiple myeloma

P-007 Prognostic impact of corticosteroid and tocilizumab use on the efficacy of chimeric antigen receptor T-cell therapy for relapsed/ refractory multiple myeloma

Real-World Use of Teprotumumab and Tocilizumab in Moderate-to-Severe Steroid-Resistant Thyroid Eye Disease

Real-World Use of Teprotumumab and Tocilizumab in Moderate-to-Severe Steroid-Resistant Thyroid Eye Disease

Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.

Meta-analysis of liver injury in patients with COVID-19.

The coronavirus disease 2019 (COVID-19) is a major public health problem threatening human health. It can lead to multiple system complications, among which liver damage is also a common complication of COVID-19. The pathogenesis of liver injury is complex and involves the interaction of multiple factors. This study aims to investigate the incidence and risk factors of liver injury in COVID-19 patients and analyze the impact of liver injury on clinical prognosis of patients, so as to provide corresponding basis for clinical diagnosis and treatment. PubMed and Cochrane Library were searched in computer to collect original studies on liver injury cases, laboratory indicators and clinical outcomes in COVID-19 patients. Articles were screened according to inclusion and exclusion criteria, and data were meta-analyzed using Stata12.0 software. A total of 49 studies, including 23,611 patients with COVID-19, had a prevalence of liver injury of 39.63%. Subgroup analysis found that patients in the Americas had the highest incidence of liver injury at 43.7% and lowest in Africa (25.99%). The vast majority of liver injury is manifested by aminotransferase or bilirubin levels greater than 1 times the upper limit of normal (49.16%). The older the age, the male, the associated chronic liver disease, and the higher the levels of white blood cells, neutrophils, and C-reactive protein, the higher the risk of liver injury. The use of hormones, hydroxychloroquine, and tocilizumab increases the risk of liver injury. Patients with concurrent liver injury have longer hospital stays, are more likely to progress to severe cases, and have a higher risk of death than patients without liver injury. The incidence of liver injury in COVID-19 patients was high, affected by age, gender, chronic liver disease, inflammatory state and medication, and patients with liver injury were hospitalized longer and were more likely to have a poor prognosis. Therefore, clinical attention should be paid to early intervention.

Adult-Onset Still's Disease in Pregnancy: Lessons Learned and an Approach to Subsequent Pregnancies.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disorder with potential for life-threatening complications in pregnancy. Recently, biologic therapeutics have been increasingly used for treatment of AOSD, but there is little available data on the treatment of AOSD in pregnancy. Here we report a 23-year-old primigravid patient with a history of AOSD who presented at 20 weeks of gestation with fever, arthralgias, rash, fatigue, and highly elevated ferritin, concerning for AOSD flare. She was treated with tocilizumab, an interleukin-6 receptor antagonist, with rapid clinical and laboratory improvement; however, she underwent iatrogenic preterm delivery at 34 weeks of gestation for fetal distress, which was attributed to placental injury. In a subsequent pregnancy, she was treated with tocilizumab throughout and had an uncomplicated term delivery with normal labs and no AOSD flare. This case highlights that the use of tocilizumab may be effective to reduce the risk of AOSD flare during pregnancy.

Tocilizumab; A Potential Remedy Against The Ever-Evolving Threat Of Coronavirus-2 (SARS-Cov-2).

Madam, Coronavirus-2 (SARS-CoV-2) is a novel positive single-strand RNA virus that is the causative agent of COVID-19, which originated in Wuhan, China, at the end of December 2019. Since the beginning of 2020, this virus has taken the world by storm, brought the globe to an absolute crawl for the last two years, and overburdened healthcare facilities in numerous countries. The Coronavirus-2 (SARS-CoV-2) virus is transmitted via aerosolized droplets, and once the virus finds itself inside the host's body, it undergoes an incubation period between 6-7 days. After the viral incubation period passes, the patient suffers from fever, cough, dyspnea, myalgia, and, in severe cases, hypoxia that requires hospitalization and mechanical ventilation.1 The pathogenesis of COVID-19 involves the dysregulation of the host immune response, which may lead to the development of acute respiratory distress syndrome in the host. The dysfunction of the host's immune response involves the hyperactivation of the humoral pathway, resulting in the overproduction of interleukin-6. Elevated levels of Interleukin-6 may lead to the development of numerous pathologies like respiratory failure, shock, and multiorgan dysfunction. This derangement of the host immune response would act as a potential target for several therapeutic agents to relieve COVID-19 symptoms.2 One such therapeutic agent is Toculimizab, which is a recombinant humanized anti-interleukin 6 receptor monoclonal antibody that functions by binding to membrane IL-6 R, thus preventing the formation of the complex with IL-6 and blocking the signal transmission. It is used in several inflammatory immune diseases such as Systemic Sclerosis, Giant Cell Arteritis, Takayasu Arteritis, etc. Tocilizumab has been shown to improve the hyperinflammatory and hypercoagulable state of COVID- 19 patients by reducing the circulating inflammatory biomarkers.3 To support the use and clinical efficacy of Tocilizumab in the hospitalized patient, a 2021 metaanalysis by Kyriakopoilous C. et al. showed the effects of Tocilizumab on mortality amongst Hospitalized COVID-19 patients and to see whether mechanical ventilation would be necessary once Tocilizumab was administered. This research was a combination of observational studies and randomized control trials. The results revealed a reduction in mortalities among 27,004 hospitalized COVID-19 patients. In the meta-analysis observational studies, there was an overall 31% decrease in mortality In the randomized control trials, there was an 11% decrease in mortality, along with a 19% decrease in the need for mechanical ventilation, showing that Tocilizumab was beneficial for all hospitalized patients.4 Continued...

ВЛИЯНИЕ ГЕМОСОРБЦИИ С ЭКCТРАКОРПОРАЛЬНОЙ АУТОГЕМОМАГНИТОТЕРАПИЕЙ В СРАВНЕНИИ С МЕДИКАМЕНТОЗНОЙ ТЕРАПИЕЙ АНТАГОНИСТАМИ РЕЦЕПТОРОВ ИЛ-6 НА КЛИНИКО-ЛАБОРАТОРНЫЕ ПАРАМЕТРЫ ПАЦИЕНТОВ С ТЯЖЕЛЫМ ТЕЧЕНИЕМ COVID-19

Background: SARS-CoV-2 infection in 10-20% of cases is characterized by hypercytokinemia, and in this context, the use of interleukin-6 (IL-6) receptor blockers, in particular tocilizumab and levilimab, is pathogenetically justified, but anticytokine hemosorption is also used in such cases. It is impossible to determine which method is preferable in patients with severe COVID-19 due to the lack of large comparative studies of medical and extracorporeal anticytokine therapies. Purpose: To evaluate the effect of hemosorption through the Нemo-Рroteasosorb hemorosorbent in combination with extracorporeal autohemomagnetic therapy and medical therapy with IL-6 receptor antagonists on the respiratory status, hemostasis, acid-base state of the blood, the detoxification function of the liver and kidneys in patients with severe COVID-19 infection. Material and methods: The clinical and laboratory findings of 102 patients with a severe course of coronavirus infection, who developed cytokine storm, were evaluated. All patients were divided into three groups: hemosorption with magnetic blood treatment («HS+MBT») (41 patients), Tocilizumab group (40 patients) and Levilimab group (20 patients). The following indicators were studied: erythrocyte count and platelet count; hemoglobin level; concentration of total protein, creatinine, urea, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibrinogen, D-dimers; acid-base state and blood gas composition. To assess the respiratory status, the respiratory index (RI), ROX index, total oxygen flow, and dynamics of the level of respiratory support were evaluated. To assess hemodynamics, mean arterial pressure and heart rate were determined, the body temperature of the patients was also measured. Results: The results obtained demonstrate that with the combined use of MBT and hemosorption through the Hemo-Proteasosorb sorbent in patients with severe COVID-19, there were no significant fluctuations in hemodynamic parameters, levels of urea, creatinine, total bilirubin, AST and ALT. At the same time, the use of tocilizumab was associated with an increase in the levels of urea, total bilirubin and ALT. In the Levilimab group there was an increase in the concentration of urea. The use of HS+MBT was associated with a decrease in the level of fibrinogen, which was noted on the next day, as well as a tendency to a decrease in D-dimers. At the same time, during the treatment with IL-6 receptor blockers, a significant decrease in the level of fibrinogen was noted only on days 6-8. The number of thromboembolic complications was also lower in the patients with extracorporeal detoxification. With HS+MBT, an increase in the respiratory status indicators (RI, ROX-index, decrease in total oxygen flow) was observed already on the next day, while in the Tocilizumab and Levilimab groups, an increase in these indicators was noted only on days 6-8. A decrease in the ROX index and the absence of dynamics in the total oxygen flow were found on the next day in both groups. In the HS+MBT group, the obtained results indicated that the given technique both prevents more significantly the transition to the next level of respiratory support and contributes to its decrease as compared to IL-6 receptor blockers. Analysis of the acid-base state of the blood following HS + MBT showed a decrease in the level of lactate and an increase in HCO3, as well as deficiency/excess of bases, which indicated compensation for metabolic acidosis. Similar results with the use of IL-6 receptor blockers were obtained only on the 6th-8th day of the study, but no normalization of the lactate concentration in the blood of patients was found at any stage. Conclusion: The use of HS+MBT has a number of advantages over the treatment with IL-6 receptor blockers, which is manifested by the absence of cardio, hepato- and nephrotoxicity, as well as more significant positive effect on hemostasis, respiratory status and acid-base status of patients.

Clinical and Microbiological Characteristics of Candidemia Cases in Saudi Arabia.

Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of Candida spp., and the associated risk factors for mortality in an academic institution in Saudi Arabia over an 18-month period. We also evaluated the susceptibility patterns of Candida blood isolates. Candidemia cases were collected from King Fahad Hospital of the University over the period between July 1st, 2020 through December 31st, 2021. They were prospectively reviewed for the preceding risk factors and antifungal (AF) susceptibility, testing results to fluconazole (FL), voriconazole (VO), itraconazole (IT), posaconazole (PO), caspofungin (CASP), anidulafungin (AND), micafungin (MYC), flucytosine (FLC) and amphotericin B (AMPB) using a broth microdilution kit (Sensititre™ YeastOne). A total of 48 candidemia isolates were included that were isolated from 43 patients. The median age of cases was 62 ± 23.3 years (60.4% males and 83% ICU patients). Independent risk factors for mortality at 30 days in candidemia patients were age, COVID-19 co-infection, and use of tocilizumab. The most commonly isolated species were C. glabrata and C. parapsilosis (22.9% each) followed by C. albicans (18.75%). AF resistance for ≥1 antifungal was detected in 39.3% of 33 cases tested, with no cross-resistance identified. Resistance rates for each AF were as follows: FL (18%), VO (6%), IT (6%), PO (9%) and AMPB (3%). No resistance was seen for echinocandins apart from one C. krusei strain showing an intermediate result for CASP. The study showed an overall high rate of non-albicans Candida, with the predominance of C. parapsilosis and C. glabrata, representing a therapeutic challenge. AF resistance rate was high which emphasizes the importance of continuing surveillance and providing accurate and reliable tools in the laboratories for rapid speciation and susceptibility testing.

Risk Factors Associated with the Development of Hospital-Acquired Infections in Hospitalized Patients with Severe COVID-19.

Recognition of risk factors for hospital-acquired infections (HAI) in patients with COVID-19 is warranted. We aimed to describe factors associated with the development of HAI in patients with severe COVID-19. We conducted a retrospective cohort study including all adult patients admitted with severe COVID-19 between March 2020 and November 2020. The primary outcome was HAI development. Bivariate and multiple logistic regression models were constructed. Among 1540 patients, HAI occurred in 221 (14%). A total of 299 episodes of HAI were registered. The most common HAI were hospital-acquired/ventilation-associated pneumonia (173 episodes) and primary bloodstream infection (66 episodes). Death occurred in 387 (35%) patients and was more frequent in patients with HAI (38% vs. 23%, p < 0.01). Early mechanical ventilation (aOR 18.78, 95% CI 12.56-28.07), chronic kidney disease (aOR 3.41, 95% CI 1.4-8.27), use of corticosteroids (aOR 2.95, 95% CI 1.92-4.53) and tocilizumab (aOR 2.68, 95% CI 1.38-5.22), age ≥ 60 years (aOR 1.91, 95% CI 1.27-2.88), male sex (aOR 1.52, 95% CI 1.03-2.24), and obesity (aOR 1.49, 95% CI 1.03-2.15) were associated with HAI. In patients with severe COVID-19, mechanical ventilation within the first 24 h upon admission, chronic kidney disease, use of corticosteroids, use of tocilizumab, age ≥ 60 years, male sex, and obesity were associated with a higher risk of HAI.

Relapse Risk and Safety of Long-Term Tocilizumab Use Among Patients With Giant Cell Arteritis: A Single-Enterprise Cohort Study.

To evaluate the safety and efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) in a large North American cohort. Patients with GCA treated with TCZ between January 1, 2010, and May 15, 2020, were retrospectively identified. Kaplan-Meier methods were used to estimate time to TCZ discontinuation and time to first relapse after TCZ discontinuation. Poisson regression models were used to compare annualized relapse rates before, during, and after TCZ use. Age- and sex-adjusted risk factors associated with relapse on and off TCZ and development of adverse events of significant interest (AESIs) were examined using Cox models. One hundred fourteen patients (60.5% female) were included with mean (SD) age 70.4 (8.2) years. Median duration from GCA diagnosis to TCZ start was 4.5 months. Median overall duration of TCZ treatment was 2.3 years. Relapse rate prior to TCZ start (0.84 relapses/person-year) was 3-fold reduced while on TCZ (0.28 relapses/person-year; P < 0.001) but increased to 0.64 relapses/person-year after TCZ discontinuation. Fifty-two patients stopped TCZ after a median of 16.8 months; 27 relapsed after discontinuation (median: 8.4 months; 58% relapsed within 12 months). Only 14.9% of patients stopped TCZ because of AESIs. Neither dose/route of TCZ, presence of large-vessel vasculitis, nor duration of TCZ therapy prior to discontinuation predicted relapse after TCZ stop. TCZ is well tolerated in GCA, with low rates of discontinuation for AESIs. However, relapse occurred in > 50% despite median treatment > 12 months. Since the duration of TCZ prior to discontinuation did not significantly affect subsequent risk of GCA recurrence, further research is needed to determine the optimal duration of therapy.

Tocilizumab Associated With Survival in Patients Hospitalized for COVID-19 Acute Respiratory Distress Syndrome and Low Urine Output.

Acute respiratory distress syndrome (ARDS) with oliguria is associated with increased mortality. Interleukin-6 (IL-6) plays an integral role in the pathophysiology of both disease processes. Patients who experience severe COVID-19 have demonstrated higher IL-6 levels compared to baseline, and use of tocilizumab has demonstrated efficacy in such cohorts. We set out to investigate the relationship between tocilizumab use, COVID-19 ARDS, low urine output, and mortality. Retrospective cohort review of adult patients aged ≥ 18 years with COVID-19 and moderate or severe ARDS, admitted to the intensive care unit (ICU) of a tertiary referral center in metropolitan Detroit. Patients were analyzed based on presence of oliguria (defined as ≤ 0.7 mL/kg/h) on the day of intubation and exposure to tocilizumab while inpatient. The primary outcome was inpatient mortality. One hundred and twenty-eight patients were analyzed, 103 (80%) with low urine output, of whom 30 (29%) received tocilizumab. In patients with low urine output, risk factors associated with mortality on univariate analysis included Black race (P = .028), lower static compliance (P = .015), and tocilizumab administration (P = .002). Tocilizumab (odds ratio 0.245, 95% confidence interval 0.079-0.764, P = .015) was the only risk factor independently associated with survival on multivariate logistic regression analysis. In this retrospective cohort review of patients hospitalized with COVID-19 and moderate or severe ARDS, tocilizumab administration was independently associated with survival in patients with low urine output ≤ 0.7 mL/kg/h on the day of intubation. Prospective studies are needed to investigate the impact of urine output on efficacy of interleukin-targeted therapies in the management of ARDS.

Effect of type of disease-modifying antirheumatic drugs on depression and anxiety of patients with rheumatoid arthritis in Saudi Arabia: a cross-sectional study.

Rheumatoid arthritis (RA) can cause depression and anxiety. This study evaluated the factors associated with depression and anxiety in patients with RA and examined the effect of conventional and biologic disease-modifying antirheumatic drugs (DMARDs). This cross-sectional study was conducted in a regional hospital in Riyadh between March and November 2022 and included 213 patients with RA. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) and data about patients' DMARDs use was obtained from the hospital's medical records. Based on the HADS scores, 35 (16.4%) and 49 (23%) patients with RA had depression and anxiety, respectively. There was a significant association between the level of depression and anxiety and the use of leflunomide and tocilizumab among patients with RA (p = 0.006 and p = 0.009, respectively). Patients with RA who took leflunomide had significantly higher scores for anxiety (β = 0.158, value of p = 0.037) when compared to patients who did not take leflunomide. Patients with RA who took etanercept showed a significantly lower depression score even after adjusting for confounders, including sociodemographic, clinical, and lifestyle factors (β = -0.189, p = 0.043). The present study highlighted the prevalence of psychiatric disorders among patients with RA and the level of depression and anxiety may differ between patients with RA depending on the type of DMARDs used. We recommend patients with RA be screened regularly for depression and anxiety to avoid further extra-articular systemic complications associated with RA.

The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Pooled analysis of cytokine release syndrome across cohorts in patients with advanced synovial sarcoma.

e14531 Background: Afami-cel is an autologous, T-cell receptor T-cell therapy engineered to target melanoma-associated antigen A4 (MAGE-A4) in human leukocyte antigen (HLA) A*02–eligible patients (pts) with advanced solid tumors. SPEARHEAD-1 (NCT04044768) is a Phase 2, two cohort, open-label trial to evaluate the efficacy and safety of afami-cel in pretreated pts with advanced/metastatic synovial sarcoma or myxoid/round cell liposarcoma. Here we report data on cytokine release syndrome (CRS) in the pts with advanced synovial sarcoma treated with afami-cel across Cohort 1 and Cohort 2. Methods: Eligible pts had advanced synovial sarcoma and were HLA-A*02 positive with MAGE-A4–positive tumors. Pts received afami-cel after lymphodepleting chemotherapy containing fludarabine and cyclophosphamide. Tocilizumab administration was permitted for Grade 1 CRS if symptoms persisted for ≥ 24 hours or if the pt had co-morbidities, and for Grade ≥2 CRS. Results: As of August 29, 2022, 72 pts with synovial sarcoma received afami-cel (n = 44 Cohort 1; n = 28 Cohort 2). Afami-cel dose range was 1.92–10.00×109 transduced T-cells. The median age was 39.5 years (range: 16–73 years), 47.2% of pts were female, 88.3% of pts were white, and tumor MAGE-A4 expression H-score was 244.5 (range: 66–300). CRS occurred in 72.2% of the pts with synovial sarcoma receiving afami-cel, including Grade 1 in 50% (36/72), Grade 2 in 20.8% (15/72), and Grade 3 in 1.4% (1/72) of pts as per American Society for Transplantation and Cellular Therapy grading. The median time to onset was 2.5 days (range: 1–5 days), and the median time to resolution was 3 days (range: 1 to 14 days). Twenty-seven of 72 (37.5%) pts received at least one dose of tocilizumab. Consistent with expectations, higher serum IL-6 levels were associated with CRS events and the indicated use of tocilizumab for management. RECIST v1.1 responses were observed in pts with and without CRS. Correlation of clinical factors and CRS with response will be presented. Conclusions: CRS was common after afami-cel administration but was mostly low grade. Administration of tocilizumab in SPEARHEAD-1 was effective in the management of CRS. Clinical trial information: NCT04044768 .

Factors Associated with Increased Risk of Major Cardiovascular Events for Patients Undergoing CAR T Therapy

Introduction: Chimeric antigen receptor (CAR)-T cell therapy use has increased exponentially following its approval for multiple indications in non-Hodgkin lymphomas, multiple myeloma, and acute lymphoblastic leukemia. While cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias are well-described and frequently encountered side effects, a significant proportion of patients experience major adverse cardiovascular events (MACE). This study investigates factors associated with increased risk for MACE. Methods: We performed a retrospective analysis of a consecutive cohort of patients treated with CAR-T therapy at our center between 2018 and 2022. Clinical, laboratory, and imaging parameters were collected. MACE were defined as acute myocardial infarction (AMI), stroke or transient ischemic attack, cardiovascular death, unstable angina, life-threatening arrhythmias, and heart failures. Data was analyzed using SPSS v23. Categorical variables were compared using univariate chi-square test. Results: A total of 126 patients were included. Of these, ten patients (12.5%) had a MACE event. Baseline characteristics including age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, CRS, ICANS, and tocilizumab use are summarized in Table. The median follow-up period was 8.9 months. Patients who experienced MACE versus no MACE had a significantly higher age at CAR-T cell therapy (74.5 years vs. 64.9 years, p = .009), higher peak C-reactive protein (CRP) with a median of 116.7 mg/dL versus 73.85 mg/dL, p = 0.006 respectively. CRS and ICANS grades were associated with MACE events (p = 0.008 and 0.005, respectively). No echocardiographic differences were found. No progression free or overall survival differences were observed in the groups (p = 0.67 and 0.16, respectively). Conclusions: Our results indicate that patients undergoing CAR-T cell therapy who are older and who experience an increased degree of inflammatory response, reflected by peak CRP level, were associated with MACE. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE in CAR-T therapy-treated patients. Prospective inflammation monitoring combined with trials incorporating anti-inflammatory strategies may mitigate the risk of MACE in this patient population. Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. G. Kaur Consultant or advisory role: SANOFI, BMS, Janssen, Cellectar, Arcellx Y. F. Madanat Consultant or advisory role: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Honoraria: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Educational grants: Blueprint Medicines and Morphosys.

ZUMA‐24: A PHASE 2, OPEN‐LABEL STUDY OF AXICABTAGENE CILOLEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA GIVEN OUTPATIENT WITH CORTICOSTEROIDS

ZUMA‐24: A PHASE 2, OPEN‐LABEL STUDY OF AXICABTAGENE CILOLEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA GIVEN OUTPATIENT WITH CORTICOSTEROIDS

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital

IntroductionOur work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. MethodsRetrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. ResultsTwo-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4–16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1–5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2–5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). ConclusionsSuperinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Early versus standard management of chimeric antigen receptor therapy toxicities and management's impact on safety and efficacy.

Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are well-documented toxicities of CAR T-cell therapy. To mitigate excessive toxicity, our center has formulated treatment protocols (early vs. standard) for timely management of CRS and ICANS with tocilizumab and/or corticosteroids. This retrospective, single-center analysis included patients treated with CAR T-cell therapy. The goal was to describe the association of two management protocols with toxicity and efficacy outcomes. Fifty-five percent of the 40 patients assigned to early management, out of which 5% and 9% developed grade 3+ CRS and ICANS, respectively. Seventy-seven percent and 41% of these patients received tocilizumab and corticosteroids, respectively. Forty-five percent of patients were stratified as standard management, out of which 0% and 11% developed grade 3+ CRS and ICANS, respectively. Seventeen percent and 28% of these patients received tocilizumab and corticosteroids, respectively. The day +90 overall response rate (ORR) for all patients was 63%, with an ORR of 89% for those managed per early management versus 50% for those managed per standard protocol. Early use of tocilizumab and corticosteroids is effective in preventing excessive CAR-T-related toxicities with no negative impact on efficacy.

Changing Trends in the Global Consumption of Treatments Used in Hospitalized Patients for COVID-19: A Time Series Multicentre Study.

To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials.

OA31 Real life experience of tocilizumab treatment for giant cell arteritis

Abstract Background/Aims Giant cell arteritis (GCA) has been revolutionised by fast track pathways that ensure early secure diagnosis. The GiACTA study provided evidence for the beneficial role of tocilizumab in the treatment of GCA and encouraged us all to reconsider the role of corticosteroids. These data relate to real life experience of the use of tocilizumab, including current status of patients after completing the initial year of treatment. In Scotland, tocilizumab was initially used for patients with relapsing disease or steroid complications. However, since 2018, the Scottish Medicines Consortium has supported use from disease onset and it has become increasingly common to consider adding at diagnosis. Methods The case notes of 23 patients treated with tocilizumab were reviewed back to 2017. Patient demographics were collated including whether cranial (C) or large vessel vasculitis (LVV) variant. The diagnosis of GCA had to be confirmed by biopsy or imaging with GCA rheumatology clinic review. Any patients who discontinued tocilizumab prior to completing one year had the reason recorded. Duration on tocilizumab was intended to be one year. Data were reviewed to capture outcomes after treatment was withdrawn. Results 2 patients with non-relapsing disease discontinued tocilizumab within the first month due to early relative neutropenia (1.4). 5 of 21 patients who completed treatment have since had additional tocilizumab treatment. 1 patient with particularly severe relapsing disease and steroid complications remains on long term tapered tocilizumab monotherapy without attempt to stop (C and LVV). 4 patients (LVV=C) flared within 1-9 months (median 6 months) and resumed with steroids and subsequent tapers; all had commenced for relapsing disease. 1 patient (C), commenced on tocilizumab at diagnosis, opted for MTX when flared. 15 remaining patients are on no steroid, methotrexate or tocilizumab and are free of disease activity as yet, but undergoing monitoring for flare (12C 3 LVV variant). Conclusion Tocilizumab is effective, limits steroid exposure and is well-tolerated by patients. The most common reason for discontinuing tocilizumab was relative neutropenia (neutrophils 1-1.4). The majority of patients discontinued tocilizumab and have not yet flared off all treatment. Cranial variant was less associated with relapse after tocilizumab treatment versus LVV. New diagnoses appear less prone to relapse off tocilizumab than patients already known to have relapsing disease prior to using tocilizumab. Patients discontinuing tocilizumab benefit from ongoing monitoring to recognise the early stages of returning disease; this would need to be provided for at least one year. Patients discontinuing treatment, their GPs and carers need advice on routes to escalate concerns about returning symptoms. Fast track services need to provide a flare service in addition to a diagnosis pathway if there is to be safety, confidence and expert support for this patient group and primary care colleagues. Disclosure L.M.M. Hutton: Other; 2022 Roche educational grant to attend BSR.