Tocilizumab Group Research Articles

Four-year follow-up of atherogenicity in rheumatoid arthritis patients: from the nationwide Korean College of Rheumatology Biologics Registry.

This study aimed to evaluate the impact of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) on lipid profile and atherogenic index of plasma (AIP) in rheumatoid arthritis (RA) patients and to compare the occurrence of dyslipidemia between patients using bDMARDs, tsDMARDs, or conventional DMARDs (cDMARDs). Data on lipid profile, AIP, and occurrence of dyslipidemia were collected from the Korean College of Rheumatology BIOlogics registry. A comparison was conducted between patients using bDMARDs (tumor necrosis factor (TNF)-α inhibitor, tocilizumab, abatacept), Janus kinase inhibitors (JAKis), and cDMARDs. The Kaplan-Meier method was used to compare the occurrence of dyslipidemia between groups, and hazard ratios (HR) were calculated using the cox proportional hazard method. The data of 917, 826, 789, 691, and 520 RA patients were eligible for analysis at the baseline, 1-year, 2-year, 3-year, and 4-year follow-ups, respectively. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were higher in the cDMARDs group, whereas AIP was comparable. During the 4-year follow-up, AIP was comparable between the groups. The occurrence of dyslipidemia did not show a significant difference when comparing the bDMARDs/tsDMARDs and cDMARDs groups (P=0.06) or the TNF-α inhibitor, tocilizumab, abatacept, JAKi, and cDMARD user groups (P=0.3). In the multivariate cox proportional hazard model, older age (HR=1.03, P=0.005) and concomitant hypertension (HR=2.21, P=0.013) were significantly associated with dyslipidemia occurrence. Long-term use of bDMARDs and tsDMARDs is relatively safe with regard to lipid profile, AIP, and the occurrence of dyslipidemia in RA patients. Key Points • The use of bDMARDs and tsDMARDs did not increase the risk of dyslipidemia than cDMARDs use in patients with RA. • AIP was comparable between bDMARDs user, tsDMARDs user, and cDMARDs user group in 4-year follow-up data. • Based on the present study, the long-term use of bDMARDs or tsDMARDs did not significantly deteriorate atherogenic lipid profile nor an increased risk of dyslipidemia in patients with RA.

“Tocilizumab-an option for patients with COVID-19 associated cytokine release syndrome: A single center experience”, a retrospective study-original article

BackgroundThe first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was diagnosed in Wuhan, China in 2019. In the first half of 2020, this disease has already converted into a global pandemic. This study aimed to find that treatment of patients with COVID-19 pneumonia with Tocilizumab or steroids was associated with better outcomes. Objectives: To analyze the effectiveness of Tocilizumab in moderate to severe Covid-19 patients based on predefined assessment criteria. Study Settings: Single-center, Fatima Memorial Hospital, Lahore. Study designQuasi-experimental. Duration of studyFrom May 12, 2020 to June 12, 2020. Patients & Methods: Sample size and techniqueSample size was 93; 33 patients were kept in the experimental group, given Tocilizumab, 8 mg/kg intravenously or 162 mg subcutaneously, and the rest of the 60 patients were given corticosteroids, methylprednisolone 80 mg/day. Consecutive sampling. Failure of therapy was labeled when patients were intubated or died, and the endpoints were failure-free survival which was the primary endpoint, and overall survival secondary at the time of discharge. ResultsA total of 93 patients were enrolled, the Tocilizumab (TCZ) group (case) and Corticosteroid (CS) group (Control). The median age was 58 years (IQR-21), 37 (39.8%) patients with diabetes mellitus, 11 (11.8%) in the TCZ group, and 26 (28%) in the CS group. On the whole, the total median hospital stay in days was 7 with IQR (4), a total of 83 (89.2%) patients recovered successfully and discharged, 27 (29%) in the TCZ group and 56 (60.2%) in the CS group. Total 10 (10.8%) patients died, out of which 6 (6.5%) belonged to the TCZ group and 4 (4.3%) belonged to the CS group The median Oxygen requirement with IQR was 8 (9) in both the groups and in total as well, p-value (0.714). ConclusionsTocilizumab is a quite effective treatment option for critically sick patients of Covid-19 by reducing their oxygen requirement drastically and so the ICU stay, median hospital stay and so the mortality as well. Clinicals trials registrationUIN # NCT04730323

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis.

Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.

Repurposed Tocilizumab in Patients with Severe COVID-19.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial

ObjectiveTo determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19).DesignRandomised, open label trial.SettingNine hospitals in Brazil, 8 May to 17 July 2020.ParticipantsAdults with...

Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis.

Retrospective, observational, multicenter, cohort study between March 15, 2020, and May 31, 2020. Using propensity score matching based on ICU admission source, C-reactive protein, Sequential Organ Failure Assessment score, vasopressor use, age, race, weight, and mechanical ventilation, patients who received tocilizumab were matched to patients who did not receive tocilizumab. Ten hospitals within the Cleveland Clinic Enterprise. Adult patients admitted to a medical, surgical, neurosciences, or mixed ICU with severe acute respiratory syndrome coronavirus 2 infection. None. Four-hundred forty-four patients were included: 342 patients (77%) did not receive tocilizumab and 102 patients (23%) received tocilizumab. Of those, 82 patients in each arm were matched. Before matching, patients who received tocilizumab had higher Sequential Organ Failure Assessment scores (6.1 ± 3.4 vs 4.7 ± 3.6), higher C-reactive protein (21.0 ± 10.2 vs 13.7 ± 9.6 mg/dL), higher frequency of intubation, vasopressor requirement, and paralytics. After matching, characteristics were more balanced and over 85% of patients required mechanical ventilation. ICU mortality was lower in tocilizumab group (23.2% vs 37.8%; risk difference, -15%; 95% CI, -29% to -1%), with more ICU-, hospital-, and vasoactive-free days at day 28 compared with those who did not receive tocilizumab. There was no difference in mechanical ventilation-free days at day 28 or development of secondary infections. Tocilizumab use was associated with a significant decrease in ICU mortality in critically ill coronavirus disease 2019 patients with severe hypoxemic respiratory failure. Future randomized controlled trials limited to tocilizumab administration in critically ill coronavirus disease 2019 patients, with severe hypoxemic respiratory failure, are needed to support these findings.

Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study.

IntroductionLittle evidence appears to exist for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state.Patients and MethodsA retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265–0.910; p = 0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.ConclusionsIn patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients and may improve their prognosis.

Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial

SummaryBackgroundAlthough targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells—the target for rituximab—in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status.MethodsThis study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28.FindingsBetween Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI −11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [–1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [–5 to 10]) were not significantly different between treatment groups.InterpretationThe results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice.FundingEfficacy and Mechanism Evaluation programme from the UK National Institute for Health Research.

Effect of tocilizumab on intensive care patients with Covid-19 pneumonia, a retrospective cohort study.

In this study, the efficacy of an IL-6 antagonist, Tocilizumab, administered in the early period was studied in intensive care patients with COVID-19 pneumonia followed by hypoxic and systemic inflammation not receiving mechanical ventilation support. Patients with COVID-19 pneumonia who have signs of hypoxia and systemic inflammation and/or who have acute bilateral infiltrates on chest radiograph and who received tocilizumab treatment were compared with the patients who received standard medical therapy. Patients who were followed up with COVID-19 pneumonia and respiratory failure between March 2020 and March 2021 were retrospectively evaluated in the study. A 400 mg - 800 mg iv dose (depending on weight) of Tocilizumab was administered. The primary endpoint was determined as intensive care unit mortality. A total of 213 patients who were admitted with respiratory failure associated with COVID-19 to our third-level intensive care unit were evaluated. Of these patients, the study was conducted with 50 patients in the tocilizumab treatment group and 92 patients in the standard treatment group. During the intensive care period, 26 patients (28.3%) in the standard treatment group and 12 patients (24%) in the group receiving tocilizumab died. The adjusted hazard ratio for mortality in the tocilizumab group was 0.39 (95% confidence interval [CI], 0.186 to 0.808; p = 0.001 by log-rank test). During the intensive care period, 22 patients (24.8%) in the standart treatment group and 16 patients (32%) in the tocilizumab group were intubated. The adjusted hazard ratio for a primary outcome intubation in the tocilizumab group was 0.71 (95% confidence interval [CI], 0.355 to 1.424; p = 0.184 by log-rank test).

Improved clinical outcomes of tocilizumab versus cyclophosphamide for IgG4-related disease: insights from a prospective IgG4-related disease registry.

Objective:To compare the clinical outcomes of patients with active immunoglobulin G (IgG) 4 related disease (IgG4-RD) receiving tocilizumab versus those receiving cyclophosphamide (CYC).Methods:This IgG4-RD registry study was a prospective cohort study conducted among patients with active IgG4-RD hospitalized at Zhongshan Hospital, Fudan University. Patients who were treated with tocilizumab or CYC along with glucocorticoids (GCs) were enrolled. All participants were followed up at the hospital clinic at 3 and 6 months after discharge. Primary clinical outcomes were measured via the IgG4-RD responder index (RI), complete response (CR), and partial response (PR), as well as side effects.Results:From January 2015 to June 2020, 29 patients enrolled. Fourteen and 15 patients were treated with tocilizumab and CYC, respectively. At the 6-month follow-up, disease activity parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgG4, and IgG4-RD RI, decreased significantly in both groups. At 6 months, tocilizumab demonstrated its superiority, with 50% of patients achieving CR in the Tocilizumab group versus 20% in the CYC group. However, no statistical significance was identified (p = 0.128). The GC dosage at 6 months was significantly lower in the tocilizumab group than in the CYC group [10 (9.4–15) mg/d versus 15 (15–15) mg/d, p = 0.025]. In the CYC group, two patients experienced lumbar vertebral compression fractures related to GCs. Other patients in both groups showed mild adverse effects.Conclusions:Tocilizumab could be a better steroid-sparing agent, with a comparable curative effect and tolerance, than CYC, in the treatment of IgG4-RD.

Prediction of Clinical Requirement of Tocilizumab Injection in COVID-19 Patients with High Chest CT Severity Score- A Retrospective Analysis

Introduction: The ongoing Coronavirus Disease 2019 (COVID- 19) pandemic has spread rapidly across the globe. Tocilizumab is a recombinant monoclonal antibody to Interleukin-6 (IL-6) receptor. An increasing number of studies across the world is reporting the use of tocilizumab in treating COVID-19 patients or at risk of developing cytokine storm. Apart from clinical and laboratory parameters, High Resolution Computed Tomographic (HRCT) chest scan is a promising tool to identify patients very early in the course of COVID-19 disease. Aim: To find whether high chest CT Severity Score (CTSS) on HRCT thorax scan predict the clinical requirement of tocilizumab injection in COVID-19 patients. Materials and Methods: In this retrospective study, during the period from May 2020 to July, 2020, 250 patients with confirmed Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) diagnosed with COVID-19 in first or repeat sample and who also underwent HRCT scan of the chest, were assigned chest CTSS. From the data obtained, patients were categorised into two groups based on mild and severe CTSS. Patients with higher CTSS have a higher future possibility of developing the cytokine storm and hence the requirement of tocilizumab can be reliably predicted. All statistical analysis was performed in IBM Statistical Package for the Social Sciences (SPSS) version 20. Results: Out of a total of 250 patients, 72 patients were given tocilizumab injection. The average CTSS was 29.8±6.38 in the tocilizumab injection group. Only 8% of patients with mild CTSS received tocilizumab injection while 60% of patients with severe CTSS received tocilizumab injection (p&lt;0.001). Out of 72 patients who received tocilizumab injection, 16.7% had mild CTSS while 83.3% had severe CTSS (p&lt;0.001). Average values of inflammatory markers like C-Reactive Protein (CRP), D-Dimer, Ferritin, Lactic De-Hydrogenase (LDH), and IL-6; were significantly higher in severe CTSS and tocilizumab group (p&lt;0.001). Conclusion: CTSS may be used as a new decisive tool in triaging in-hospital COVID-19 patients. Categorising patients in mild and severe CTSS early in the disease course, even before the marked worsening of laboratory parameters and development of cytokine storm may help initiate early treatment and thereby save many lives.

Comparative study of monoclonal anti-IL6 antibodies in severe new coronavirus disease COVID-19 patients. Retrospective cohort study

Introduction. Novel coronavirus infection (COVID-19) is characterized by systemic hyper-inflammation with elevated inflammatory cytokines, that has been recognized as a leading cause of severity COVID-19. Many clinical evidences have indicated the importance of anti-inflammatory immunomodulation therapy in severe COVID-19, especially anti-IL6 monoclonal antibodies. Objectives. Comparative study of the monoclonal anti-IL6 antibodies in severe COVID-19 patients. Materials and methods. Single-center observational retrospective cohort study included three groups of hospitalized COVID-19 patients treated with one-dose tocilizumab (Group 1, 200 patients), levilimab (Group 2, 100 patients), and olokizumab (Group 3, 100 patients). Main parameters at baseline included: C-reactive protein serum concentration, and lung CT score. End-points included: sepsis and in-hospital death. Results. No significant difference in demographic characteristics and main parameters at baseline were found. A comparative analysis of clinical outcomes in the group revealed a statistically significant increase in the risk of sepsis and death in the levilimab group compared with the tocilizumab and olokizumab groups. When comparing the “Lethal outcome” indicator depending on the drug, we were unable to identify significant differences (p = 0.259, Fisher’s exact test for multi-field tables), as in the “Sepsis” outcome (p = 0.587, Fisher’s exact test for multi-field tables) When comparing tocilizumab for s/c and i.v. administration, we were unable to identify statistically significant differences (p = 0.293, Exact test Fisher) The odds of sepsis in the subcutaneous group were 2.28 times lower than in the intravenous group; the odds differences were not statistically significant (OR = 0.44, 95% CI 0.1–1.88). Conclusions. The use in patients with severe COVID-19 of different drugs of monoclonal antibodies against interleukin 6 did not reveal significant differences in deaths between tocilizumab, levilimab and olokizumab. The identified differences between the drugs in the incidence of sepsis and death require further randomized controlled trials.

Longitudinal treatment responsiveness on plasma neurofilament light chain and glial fibrillary acidic protein levels in neuromyelitis optica spectrum disorder.

Background:Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood.Objective:To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD.Methods:pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab (n = 29), rituximab (n = 23), oral prednisone (n = 16), and oral azathioprine or mycophenolate mofetil (n = 4).Results:NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2–39.3) versus 11.5 (7.0–23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6–406.5) versus 68.7 (59.4–80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age (p = 0.017), Expanded Disability Status Scale (EDSS) score (p = 0.002), and recent relapses (p < 0.001). Baseline pGFAP concentration was also associated with EDSS (p < 0.001) and recent relapses (p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(β), 0.65; 95% confidence interval (CI), 0.56–0.75; p < 0.001; rituximab, exp(β), 0.79; 95% CI = 0.68–0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(β), 0.64; 95% CI, 0.51–0.80; p < 0.001; rituximab, exp(β), 0.77; 95% CI, 0.61–0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06–17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94–21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4–131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8–192.7) pg/mL; p < 0.001].Conclusion:pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

562. Tocilizumab for the Treatment of Severe COVID-19: A Retrospective, Multi-Center, Case-Matched Series

BackgroundAt the time of this writing, there is no FDA approved medication for the treatment of COVID-19. One medication currently under investigation for COVID-19 treatment is tocilizumab, an interleukin-6 (IL-6) inhibitor. It has been shown there are increased levels of cytokines including IL-6 in severe COVID-19 hospitalized patients attributed to cytokine release syndrome (CRS). Therefore, inhibition of IL-6 receptors may lead to a reduction in cytokines and prevent progression of CRS. The purpose of this retrospective study is to utilize a case-matched design to investigate clinical outcomes associated with the use of tocilizumab in severe COVID-19 hospitalized patients.MethodsThis was a retrospective, multi-center, case-matched series matched 1:1 on age, BMI, and days since symptom onset. Inclusion criteria included ≥ 18 years of age, laboratory confirmed positive SARS-CoV-2 result, admitted to a community hospital from March 1st – May 8th, 2020, and received tocilizumab while admitted. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, total mechanical ventilation days, mechanical ventilation mortality, and incidence of secondary bacterial or fungal infections.ResultsThe following results are presented as tocilizumab vs control respectively. The primary outcome of in-hospital mortality for tocilizumab (n=26) vs control (n=26) was 10 (38%) vs 11 (42%) patients, p=0.777. The median hospital length of stay for tocilizumab vs control was 14 vs 11 days, p=0.275. The median days of mechanical ventilation for tocilizumab (n=21) vs control (n=15) was 8 vs 7 days, p=0.139, and the mechanical ventilation mortality was 10 (48%) vs 9 (60%) patients, p=0.463. In the tocilizumab group, for those expired (n=10) vs alive (n=16), 10 (100%) vs 7 (50%) patients respectively had a peak ferritin > 600 ng/mL, and 6 (60%) vs 8 (50%) patients had a peak D-dimer > 2,000 ng/mL. The incidence of secondary bacterial or fungal infections within 7 days of tocilizumab administration occurred in 5 (19%) patients.ConclusionThese findings suggest that tocilizumab may be a beneficial treatment modality for severe COVID-19 patients. Larger, prospective, placebo-controlled trials are needed to further validate results.DisclosuresChristian Cheatham, PharmD, BCIDP, Antimicrobial Resistance Solutions (Shareholder)

553. Critically Ill patients Receiving Tocilizumab Compared With Those Not Receiving Tocilizumab for Treatment of COVID-19

BackgroundBackground::Immune modulation in patients with clinical features suggestive of a cytokine release syndrome (CRS) has become a pharmacologic target for potential treatment of COVID-19 and prevention of ARDS. Tocilizumab is an IL-6 receptor blocker FDA-approved for chimeric antigen receptor (CAR) T cell-induced severe or life-threatening CRS. The objective of this study was to describe clinical outcomes associated with tocilizumab compared with those not receiving tocilizumab in critically ill patients with severe COVID-19.MethodsMethods:Retrospective case series of 49 adult patients admitted to an intensive care unit with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients receiving tocilizumab were compared with those not receiving tocilizumab. The primary outcome was clinical improvement (decrease in supplemental oxygen requirement, discharge from ICU, or live discharge from hospital). Secondary endpoints included mortality and frequency of extubation. All comparative endpoints were assessed at 2 weeks after ICU admission.ResultsResults:49 patients were identified with SARS-CoV-2 who were admitted to an ICU, 16 received tocilizumab. Baseline characteristics were similar; most were African American males with comorbidities such as obesity, cardiovascular disease, and diabetes. The time from symptom onset to positive test and subsequent intubation were similar (4 and 7 days, respectively). 75% received one dose (all received 8 mg/kg). The median time from symptom onset to tocilizumab administration was 11 days.In patients receiving tocilizumab compared with those not receiving tocilizumab, there were similar rates of clinical improvement (44% versus 61%, p=0.27), extubation (31% versus 45%, p=0.60), and mortality (18% versus 19%, p >0.99, respectively). 81% of the tocilizumab group had resolution of fever and 75% had improvement in C-reactive protein levels.ConclusionConclusion:In this study of patients with progressed disease, outcomes were similar regardless of receipt of tocilizumab. Randomized controlled trials are needed to assess the impact of earlier administration and identify clinical characteristics to assist with selection of appropriate patients who may benefit from tocilizumab.Disclosures All Authors: No reported disclosures

Adult-onset still's disease and treatment results with tocilizumab.

Adult-onset Still's disease (AOSD) is a rare and non-familial auto-inflammatory disorder. Increased levels of IL-6 and other pro-inflammatory cytokines have been shown in AOSD. To evaluate the efficacy and safety profile of tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody, in AOSD. Thirty-nine patients followed up with the diagnosis of AOSD between 2013 and 2019 were retrospectively evaluated and the 16 patients (10 Female/6 Male) treated with TCZ for refractory AOSD were included in the study group. Among the remaining 23 patients 16 had non-biological treatments and had no important complications at the presentation. TCZ was given to patients at a dose of 4-8mg/kg every 4weeks. Patients were evaluated after 3-6months of TCZ treatment for side effects, inflammatory and clinical response and concomitant treatments. In TCZ (+) patients, the majority were female (62.5%), the mean age at disease onset was 38.5±17.9 (20-81) years, and the most common symptoms and signs were myalgia (81.3%), fever (81.3%) and skin eruptions (75%). There was no difference between TCZ (+) and TCZ (-) groups for age, sex and clinical presentations. There was a significant decrease in dose of prednisolone, sedimentation rate, leucocyte count, C-reactive protein and ferritin levels and improvement in all clinical complaints after TCZ treatment. There were no relapses during the treatment. Three patients are in remission and under follow-up without any treatment after cessation of TCZ (4months-3years). No exacerbation of disease yet seen in those patients. TCZ is an effective and well-tolerated treatment option for treatment resistant AOSD and contributes to the glucocorticoid-sparing. Since TCZ is a new drug in the treatment of AOSD, further studies are needed to assess whether the complications reported during the treatment are because of TCZ or natural course of the disease or coincidental findings.

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

BackgroundCoronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.MethodsWe randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28.ResultsA total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P=0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, –5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group.ConclusionsIn hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.)

Experience With the Use of Baricitinib and Tocilizumab Monotherapy or Combined, in Patients With Interstitial Pneumonia Secondary to Coronavirus COVID19: A Real-World Study.

ObjectiveTo describe the experience of treatment with baricitinib (BARI) and/or tocilizumab (TCZ), in monotherapy or combined, in patients admitted for interstitial pneumonia secondary to COVID19, and for 30 days after discharge.MethodsMedical records of patients admitted with COVID19 and IP with PaO2/FiO2 < 300, treated with BARI and/or TCZ, and compared with patients who did not, were retrospectively reviewed.ResultsSixty patients were included; 43 (72%) are males, mean age 67 (SD: 14) years (<50 years: 17%; 51–70: 30%; >70: 53%), with 8.5 (SD: 1) days of symptoms. Sixteen (27%) patients required ICU (94% in <70 years). Fifteen (25%) patients died, 67% in >70 years; 11 (18%) patients died in the first 15 days of admission and 4 (7%) between days 16 to 30. Twenty-three (38%) patients received BARI, 12 (52%) monotherapy (Group 1), during 6 (SD: 2.6) days on average, none required ICU and 2 (17%) died. Thirty-one (52%) patients received TCZ, 20 (33%) as monotherapy (Group 2), 16 (52%) patients required ICU and 4 (20%) died. In the 11 (18%) patients who received BARI (2.8 [SD: 2.5] days average) and TCZ combined (Group 3), 3 (27%) required ICU and died. There were no severe side effects in BARI or TCZ patients. In the 17 (28%) patients who received neither BARI nor TCZ (Group 4), none required ICU and 6 (35%) died. Mean (SD) PaO2/FiO2 at admission between groups was respectively: 167 (82.3), 221 (114.9), 236 (82.3), 276 (83.2).ConclusionTreatment with BARI and TCZ did not cause serious side effects. They could be considered early in patients with NI secondary to COVID19 and impaired PaO2/PaFi.

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial

ObjectivesNo immunomodulatory drug has been approved for primary Sjögren’s syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients...

A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019.

Observational cohort study of patients hospitalized with coronavirus disease 2019 between March 1, 2020, and April 24, 2020. A propensity-matched (1:1) analysis was used to compare patients who received tocilizumab to controls who did not. Competing risk survival analysis was used to determine the primary outcome of time to mortality, and adjusted log-linear and logistic regression for secondary outcomes. Three hospitals within the NYU Langone Health system in New York. Consecutive adult patients hospitalized with coronavirus disease 2019. Tocilizumab 400-mg IV once in addition to standard of care or standard of care alone. Data from 3,580 severe acute respiratory syndrome coronavirus 2 positive qualifying hospitalized patients were included, of whom 497 (13.9%) were treated with tocilizumab. In the analysis of tocilizumab-treated patients and matched controls, fewer tocilizumab-treated patients died (145/497, 29.2%) than did controls (211/497, 42.4%). In the adjusted competing risk regression model, tocilizumab therapy was associated with improved survival relative to controls (hazard ratio = 0.24, 95% CI = 0.18-0.33, p < 0.001). Tocilizumab-treated patients and controls had similar adjusted time to discharge from hospital (hazard ratio = 0.96, 95% CI = 0.78-1.17, p = 0.67). However, they had longer adjusted ICU length of stay (rate ratio = 3.1, 95% CI = 2.5-3.7, p < 0.001) and a higher adjusted infection rate (odds ratio = 4.18, 95% CI = 2.72-6.52, p < 0.001) than controls. Tocilizumab therapy was associated with significantly improved survival in coronavirus disease 2019 patients. This survival benefit was associated with increased ICU length of stay and increased infection rate, even as more patients in the tocilizumab group were rescued from rapid death. A prospective, randomized, placebo-controlled trial is needed to confirm these findings.