Tocilizumab Therapy Research Articles

Efficacy of tocilizumab treatment in COVID-19 patients with cytokine release syndrome

Background/Aim: Cytokine release syndrome, a potentially life-threatening condition in SARS‐CoV‐2 (COVID-19) patients, plays a critical role that may lead to the prioritization of tocilizumab (TCZ) in the treatment of this disease. We aimed to present our TCZ-treated SARS‐CoV‐2 patients’ data that might help and guide clinicians in dealing with this infectious disease in their daily practice and research. Methods: This is a retrospective multicenter cohort study from two Turkish pandemic centers. A total of 5165 patients’ data who were hospitalized due to SARS‐CoV‐2 pneumonia from March 16 to May 20, 2020 were screened and 72 patients treated with TCZ were included in the study. We evaluated patients' demographic data, laboratory and imaging studies, and clinical outcomes and the effect of TCZ treatment on patients' laboratory and clinical results. Results: O2 saturation levels significantly increased, and fever significantly decreased on the 5th day after TCZ therapy compared to before its initiation (P=0.001, P=0.010, respectively). The decrease in troponin-I, creatinine, LDH, fibrinogen, CRP, procalcitonin, CK, and ferritin levels after TCZ therapy were significant (P0.05 for all). Importantly, we found a significant increase in mortality rates in patients who received azithromycin, oseltamivir, and ascorbic acid treatments compared to those who did not receive those treatments (P

P0741 / #1916: MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN (MIS-C) ASSOCIATED WITH COVID-19 INFECTION PRESENTING WITH STEVEN JOHSON SYNDROME

AIMS & OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is related to the SARS-CoV-2 Steven Johnson Syndrome (SJS) can also cause multisystem involvement as a result of serious inflammatory reaction. We reported two pediatric cases of COVID-19 associated MIS-C syndrome presenting with SJS. METHODS: We reported two pediatric cases of COVID-19 associated MIS-C syndrome presenting with SJS. RESULTS: Both patient presented with fewer, prominent skin and respiratory findings. Skin punch biopsy showed SJS. Triggering infection agents were H. influenza and COVID-19. Laboratory data showed a leukocytopenia with lymphopenia and eleveated acute phase reactants and impaired liver and kidney function. Broad-spectrum antibiotic therapy and variable teratments including immunomodulators, plasma exchange were given. Despite all treatments, severe hypoxia continued, they were put on the veno-venous extracorporeal membrane oxygenation (VV-ECMO). The first patient died surgical cannula complicaiton on the 17thday of VV-ECMO. Despite effective ECMO support tissue hypoxia became prominent and second patient died on the 40rdday. CONCLUSIONS: It is noteworthy that there are similar immunopathological mechanisms between SJS with COVID 19 infection. This is the first cases of SJS associated with COVID-19. While the cytokine storm of the first patient were benign and under control, our second case had severe multiorgan failure and hyperinflammatory status of the patient could not be controlled with intensive immunmodulatory treatments. The most noticeable difference 2 patients was that the first patient received tocilizumab treatment in the early period. This suggests that tocilizumab therapy should be given early in both MIS-C and SJS-related cytokine storm management.

Tocilizumab for Severe COVID-19 Pneumonia: Experience from 5 Geriatric Chinese Patients with 6 Months Follow-up.

To enable physicians to understand the efficacy and safety of Tocilizumab (TCZ) in patients with severe coronavirus disease-2019 (COVID-19). We respectively reviewed the clinical records, laboratory results, and chest computed tomography (CT) scans of 5 geriatric patients with severe COVID-19 treated with TCZ during their inpatient hospitalization period in Wuhan from February 08, 2020 to April 04, 2020. The survival status of the patients in the third and the sixth month after being discharged was followed up and recorded. On the fourteenth day after TCZ administration, periphery oxygen saturation rate (SpO2) returned to normal in 4 patients. The serum Interleukin-6 (IL-6) levels altered in five patients after TCZ infusion. One patient rapidly progressed to acute respiratory distress syndrome (ARDS) and died of multiple organ failures eventually. The other 4 patients were cured and discharged from the hospital. During the inpatient hospitalization period, two patients suffered from virus shedding periods (VSPs) delay, and one patient had mild upper respiratory tract infection. One patient died of esophageal carcinoma one month after being discharged. The other 3 patients survived despite mild cough and insomnia. Serum-specific IgG type antibody titer was decreased in one patient. Six months after being discharged, the other three patients were in good condition. TCZ may be an efficient therapeutic option for patients with COVID-19. However, the possibility of VSPs delay, secondary infection, serum protective antibody tilter attenuation, and long-term survival status should be addressed before TCZ therapy initiation.

Durability of Response to Tocilizumab Therapy in Rheumatoid Arthritis: Data from the US-Based Corrona Rheumatoid Arthritis Registry.

IntroductionUnderstanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice. MethodsTCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan–Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability.ResultsAmong 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score.ConclusionsMedian durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA.Trial RegistrationClinicalTrials.gov identifier, NCT01402661

Steroid-Resistant Graves' Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience.

This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO.

Multiplex analysis of laboratory biomarkers in assessing effectiveness of tocilizumab in treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis (synovitis) and that can involve other tissues and organs. The use of biologics in clinical practice, including humanized monoclonal antibodies (IgG1) to interieukin-6 (IL-6R) receptors, it's the cause to search for predictors of response to this therapy. The aim of this study was to determine the relevance of multiplex cytokine analysis in evaluating the effectiveness of tocilizumab (TCZ) in RA. Materials and methods . We examined serum samples from 43 patients with RA. The comparison group was 297 healthy subjects matched by gender and age. Serum concentration of IgM and IgA rheumatoid factors (RF) and C-reactive protein (CRP) in serum was measured by immunonephelometry; of antibodies to cyclic citrullinated peptide (anti-CCP), antibodies to modified citrullinatedvimentin (anti-MCV), matrix metalloprotinase-3 (MMP-3) - by enzyme-linked immunosorbent assay; of cytokines - by xMAP technology. Results. At week 4 on TCZ therapy, patients with RA had a decrease serum levels of CRP, IgM RF, AMCV, MMP-3; on 8th - ESR, CRP, IgM and IgA RF, anti-CCP and anti-MCV, on the 24th - of all biomarkers, excluding anti-CCP. At 4th, 8th, 24th weeks of therapy, there was a decrease in serum levels of all studied cytokines (excluding IL-6 at 4th week and IL- 1ra at 8th and 24th weeks). The most associated factors witch effectiveness of TCZ are: MMP-3 (AUC0.7), anti-CCP (0.7) and VEGF (0.7). A predictive model based on the assessment of serum levels of this biomarkers can predicting the clinical response to TCZ in RA (AUC = 0.85; CI: 0.7-1.0). Conclusion. The data about association of basal serum concentrations of anti-CCP, MMP-3 and VEGF with the response in RA patients, made it possible to create a multiparameter index for predicting the TCZ effectiveness.

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.

Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment.

Background and AimTo investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis.MethodFrom January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded.ResultsSeven patients were HBsAg+ (7.2%), 64 were HBsAg−/HBcAb+ (65.9%), and 26 were HBsAg−/HBcAb− (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg−/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up.ConclusionsTocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg−/HBcAb+ patients, strict monitoring is necessary.Electronic supplementary materialThe online version of this article (10.1007/s10620-020-06725-1) contains supplementary material, which is available to authorized users.

Outcome Comparison Between Tocilizumab Alone Vs Tocilizumab Followed by Intravenous Immunoglobulin (IVIG) Group in Critical COVID-19 Disease

Currently, COVID-19 is one of the most pressing healthcare problems across the world. With no definitive pharmacological guidelines, multiple drugs were used to treat critical patients with little success. of Tocilizumab, a monoclonal antibody has shown some role in the treatment of Covid-19 infection. The study was a cross-sectional prospective observational study. It was conducted in the COVID-19 Intensive Care Unit (ICU) of Liaquat National Hospital and Medical College, and National Medical Centre Karachi. The study was conducted from 15^th June 2020 to 31^st July 2020. Objective of the study was to compare the outcomes of severe to critical COVID-19 patients with established Cytokine release Syndrome (CRS), who received Tocilizumab with the group received Tocilizumab followed by intravenous immunoglobulins (IVIG). Two groups were made with one receiving Tocilizumab alone while the other received IVIG after Tocilizumab. Comparison was then made based on frequency of mortality as well the need of mechanical ventilation and its range of days. In results 4 (15.4%) patients in Tocilizumab only group died while Tocilizumab followed by IVIG treated group had 10 (38.46%) deaths. 20 (76.9%) patients needed mechanical ventilation in Tocilizumab only group while Tocilizumab followed by IVIG treated group consisted of 23 (88.46%) patients. This concludes that the group with only Tocilizumab therapy has better outcome as compare to the group who received both Tocilizumab and intravenous immunoglobulins.

Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection: a Systematic Review with Meta-analysis.

With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries (p < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C.Supplementary InformationThe online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.

Efficacy, safety, and adherence of tocilizumab therapy in elderly patients with rheumatoid arthritis: A real-world observational study

Objective: We evaluated the efficacy, safety, and drug survival rate of tocilizumab in the elderly patients with rheumatoid arthritis (RA). Methods: This study was conducted in 108 RA patients who started tocilizumab between 2008 and 2018. The patients were divided into a young group (&lt;65 years) and an elderly group (≥65 years). The efficacy, safety, and drug survival rate of tocilizumab were compared between the two groups. Results: At baseline, there were no significant differences between the elderly ( n = 45) and the young group ( n = 63) in RA duration, percentage of biologic-naïve, and RA disease activity. Health Assessment Questionnaire-Disability Index (HAQ-DI) was higher, renal function was worse, and frequency of using methotrexate was lower in the elderly group. Tocilizumab demonstrated similar efficacy in the elderly and the young group with Clinical Disease Activity Index and HAQ-DI. Compared with baseline, the frequency of steroid use was lower at one year after initiation of tocilizumab in both groups. There was no significant difference between the groups in the drug survival rate of tocilizumab for three years. Discontinuation rates of TCZ due to toxic adverse events were similar between the two groups. Conclusions: The efficacy, steroid-sparing effect, and safety of tocilizumab therapy, as well as the drug survival rate for three years, were not inferior in elderly RA compared to young RA patients.

Evaluation of Hepatitis B Seroprevalence and Hepatitis B Reactivation Frequency in Rheumatology Patients Using Biological Drug Therapy

Objective: The presence of hepatitis B virus (HBV) infection in patients using biological drug therapy may cause reactivation. There is insufficient data on the frequency of HBV reactivation, especially after the use of new biological drugs such as tofacitinib, tocilizumab, and secukinumab. This study aims to examine HBV seroprevalence in rheumatology patients using biological drug therapy and investigate the frequency of reactivation in patients with previous HBV infection. Methods: The charts of 275 patients who were followed up in the rheumatology department and used biological drug therapy were examined to evaluate the HBsAg, anti-HBc IgG, and anti-HBs test results. The frequency of reactivation was investigated by examining the HBV DNA test results before and after the biological drug therapy and the alanin aminotransferase test results were checked throughout the biological drug therapy in anti-HBc IgG-positive patients. Results: Among the patients, HBsAg was positive in 0.4%, anti-HBs in 34.4%, and anti-HBc IgG in 25.1%. The reactivation frequency was investigated in 53 biological drug therapies applied in 41 patients. The use of prophylactic antiviral drugs, where reactivation was evaluated, was found as 28.6% in TNF inhibitors, 100% in rituximab, 75.0% in tofacitinib, 0% in tocilizumab, 50% in abatacept, and 0% in secukinumab. Reactivation was detected in one of the fifty-three biological drug therapies. The reactivation case was a patient with isolated anti-HBc IgG and initial HBV DNA tests positive, using tocilizumab and cortisone, and not using entecavir prophylactic treatment regularly. Conclusions: The frequency of previous HBV infection is high in patients using biological therapy. Although prophylactic antiviral drug therapy for HBV has not been used frequently during the use of biological drug therapies other than rituximab in anti-HBc IgG positive patients, reactivation is rare. The risk of reactivation may be low in those receiving tofacitinib and secukinumab therapy and high in those receiving tocilizumab therapy.

The Effect of Prognostıc Factors and Potentıal Treatment Regımens on Fatality Covid-19 Patıents

The ongoing outbreak of the coronavirus disease 2019 (COVID-19), as named by the World Health Organization, has millions of confirmed cases worldwide and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by the International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache, and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. This study aimed to know the effects of clinical and laboratory features on investigated death. The diagnosis was based on typical findings in thoracic computed tomography (CT) and positive results of the Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2. The demographic characteristics of COVID-19 patients treated, accompanying comorbid conditions and laboratory criteria (blood lymphocyte counts, C Reactive Protein (CRP), D-dimer, Interleukin 6 (IL-6), blood neutrophil count/lymphocyte counts) were collected retrospectively. The results show that 121 cases, 66 (54.54%) were male, 55 (45.46%) were female, and the mean age was ± Std (Min-Max), 59.63 ± 17.4 (22-91). Neutrophil percentage (p = 0.027), neutrophil / lymphocyte ratio (NE / LE) (p = 0.028), CRP (p = &lt;0.001), PCT (p = 0.004), D dimer (p = 0.021) and IL 6 (p = 0.047) in patients with a fatal course, higher values were found than those recovered. Blood lymphocyte count (p = 0.001) and percent (p &lt;0.001) were lower. Number of blood white spheres (p = 0.010), blood neutrophil counts (p = 0.001) and percentage (p &lt;0.001), NE / LE (p0.001), CRP (p &lt;0.001), PCT (p = 0.003) and IL -6 (p &lt;0.001) levels were higher in patients with severe clinical findings than in mild cases. The case death rate was observed as 9%. Covid-19 patients should consider blood neutrophil percentage, blood lymphocyte count, blood lymphocyte percentage, NE / LE, CRP, D dimer, and IL 6 values as an early warning in terms of prognosis. More experience was needed to assess the benefits of immune plasma, tocilizumab, IVIG treatments, and remdesivir therapy recently introduced to the treatment protocol.

544. Severe COVID-19 in Children and Young Adults in the Washington DC Metropolitan Region

BackgroundChildren and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant.MethodsThis observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children’s National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical recordsResultsOf 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARS-CoV-2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies.ConclusionAlthough children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge.DisclosuresAndrea Hahn, MD, MS, Johnson and Johnson (Consultant)

550. Clinical impact of Tocilizumab therapy in SARS-CoV-2 respiratory infections in ICU and non-ICU patients

BackgroundTocilizumab (TCZ) is a monoclonal antibody against the interleuikin-6 receptor which is potentially beneficial in COVID-19 induced cytokine release syndrome (CRS). However, there are limited studies showing anti-inflammatory effect and clinical benefit of TCZ in COVID-19 patients. This retrospective study examines treatment responses of criteria based TCZ therapy for SARS-CoV-2 respiratory infection for ICU vs. non-ICU patients.MethodsWe established institutional criteria to identify patients at risk of CRS from COVID-19. Patients were included if they received at least 1 dose of TCZ and were admitted for at least 72 hours. Primary endpoint was to assess clinical improvement (CI) at the end of admission. CI was defined by extubation, downgrade from ICU, discharged or improvement in Clinical Ordinal Scale by 2. Secondary endpoint of the study was to assess inpatient mortality (IM) and risk factors associated with IM. Subgroup analysis included impact of early (< 96 hours) vs late (≥ 96 hours) TCZ therapy on IM.ResultsBetween March 25 to May 6, 2020, 170 patients met criteria and received TCZ. There were 83 non-ICU patients and 87 in the ICU. Forty five patients needed invasive mechanical ventilation (IMV). ICU patients tended to be obese, receive 2 doses of TCZ and have longer length of stay. Overall CI was seen in 71% of patients. CI was higher in non-ICU vs ICU patients (85.5% vs 57.5%, P=0.002). Overall IM was 18.8%; however, IM was lower in non-ICU vs ICU patients (8.4% vs 28.7%, P=0.0014). IM was higher in patients on IMV vs. non-IMV (30% vs 15.4%, P=0.03). Risk factors of ICU admission, BMI ≥ 30 kg/m2 and AKI were associated with higher risk of IM. Many IM patients were made comfort care. No differences were observed in early vs late TCZ therapy on inpatient mortality, but there was a trend toward lower mortality with early TCZ.COS Review of Tocilizumab Patients ConclusionTCZ is an effective treatment option in patients with SARS-CoV-2 patients at risk of CRS. Patients receiving TCZ in non-ICU setting had a better response to treatment compared to ICU patients. Obesity and AKI were associated with higher risk of mortality, but there was no statistical difference in early vs late therapy. Further studies with control group and larger sample size are warranted.Disclosures All Authors: No reported disclosures

Monitoring neutrophil-to-lymphocyte ratio in patients with coronavirus disease 2019 receiving tocilizumab

Monitoring neutrophil-to-lymphocyte ratio in patients with coronavirus disease 2019 receiving tocilizumab

Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review

BackgroundMyelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD. ObjectiveTo summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale. MethodsThis is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management. ResultsTen total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months. ConclusionsTocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.

Неспецифічний аортоартеріїт (хвороба Такаясу)

На клінічному прикладі перебігу хвороби Такаясу (неспецифічного аортоартеріїту) у молодої жінки розглянуто особливості клінічної симптоматики, складнощі діагностики цього захворювання. Особлива увага надана візуалізації ураження судин і оцінці динаміки змін у судинах у міру прогресування хвороби. Докладно представлені зміни в лабораторних показниках – у зіставленні з терапією, що застосовувалася. Проведено аналіз даних літератури щодо терапії захворювання. Підкреслено обмеженість даних плацебоконтрольованих досліджень щодо ефективності традиційних препаратів, які модифікують перебіг захворювання. Лікар має можливість спиратися тільки на результати обсерваційних досліджень або не-плацебоконтрольованих досліджень. Також усі проведені дослідження виконувалися за участю дуже малої кількості пацієнтів. Наведено послідовність призначення терапії, першою ланкою якої є глюкокортикоїди. Наголошується, що досягнення ремісії при ізольованій терапії глюкортикоїдами спостерігається у 50 % пацієнтів. За оновленими рекомендаціями EULAR, після підтвердження захворювання терапія має бути ініційована негайно, рекомендована стартова доза преднізолону (або еквіваленту) – 40–60 мг. Після досягнення контролю над захворюванням рекомендується поступове зниження дози до цільової 15–20 мг/добу впродовж 2–3 місяців і через 1 рік до 10 мг/добу. Наступним етапом призначають неглюкокортикоїдний імунодепресант, щоб забезпечити як «стероїдзбережний» ефект, так і триваліший контроль захворювання. Усі наявні відомості про ефективність метотрексату, мофетилу мікофенолату, циклофосфаміду, лефлуноміду й азатіоприну отримано з відкритих проспективних або ретроспективних досліджень, проведених з обмеженою кількістю учасників. Інгібітори фактора некрозу пухлини α і тоцилізумаб рекомендовані як препарати терапії другої лінії. Задовільна клініко-лабораторна відповідь спостерігалася більше ніж у 80 % пацієнтів, що отримували терапію тоцилізумабом. У цьому клінічному випадку використано тоцилізумаб і детально описано ефекти препарату при лікуванні протягом 8 місяців. Імунобіологічна терапія тоцилізумабом була асоційована з доброю клініко-лабораторною відповіддю, зменшенням стенозування судин, поліпшенням самопочуття пацієнтки.

Tocilizumab controls bone turnover in early polymyalgia rheumatica.

This study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR). Twenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients. PMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P< 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P=0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r=0.255 at W0 versus r=0.641 in healthy controls) and its correction after treatment (r=0.760 at W12 and r=0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy. Control of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.

Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is independent of the number of prior used TNF inhibitors: A systematic review and metaanalysis

To investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents. We performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus≥2 bDMARDs. The study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR=1.3; 95% CI: 1.2-1.5) and low activity disease (RR=1.3; 95% CI: 1.2-1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested. Disease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12months of treatment, suggesting that the response occurs independently of the number of prior TNFis.