ABSTRACT
BackgroundGCA is a critically ischemic large vessel vasculitis, varying in extent, severity and outcomes, hence requires disease stratification using clinical, laboratory and imaging parameters, for targeted management. Although DMARDs are used, the effectiveness in real life, such adjuvants remain un-elucidated. We performed a prospective, multi centre cohort study of new GCA stratified into remitting, relapsing, refractory, ischemic disease.ObjectivesWe assessed prognostic factors and compared critical outcomes such as remission with glucocorticoid (GC) monotherapy versus GC plus DMARDs in the first 12 months.MethodsHAS GCA study (1) recruited consecutive patients with new onset GCA from 7 centres (UK, Italy, Spain, Netherlands). diagnosis was confirmed used a modified GiACTA criteria at 6 months follow up. All underwent ultrasound (bilateral common, parietal, frontal temporal arteries, and axillary arteries) using accepted standard cut-off values [2]. GCA patients had US at baseline,1,3,6,12 months and halo count (HC) and Halo score (Temporal TAHS, axillary AAHS, total THS) assessed [3]. The primary outcome- remission at 12 months (absence of signs/symptoms, CRP<5 mg/dl, prednisolone < 5 mg daily). Results are reported as descriptive statistics.Results229 participants included in the study (GCA- 84 (36.68 %) (Figure 1). Study recruited during Covid pandemic,73 completed,11 lost to follow-up (died -7, withdrawn-4). The deceased/withdrawn patients (compared to completers) were older (80 v74 yrs, p=0.018), preponderantly male (73% v 36%, p=0.043) with visual symptoms (91% v 49%, p=0.010) partial/total sight loss (55% v 21%, p=0.024), lower CRP (21 v 68, p=0.061) and ESR (42 v 62, p= 0.317).Of 73 completers 36 required early DMARDs (<12 weeks) for refractory/relapsing/ischemic/GC related AEs. This group had more LV involvement (50% v 11%, p=0.0003), Remission attained at 12 months 32/36 (89%) in DMARD group was comparable to the remitting GC monotherapy group 33/37 (89%) with comparable cumulative GC doses (Figure 1, Table 1).At 12-months follow up, median TAHS, AAHS and THS reduced from 13 to 3, 12 to 9 and 21.5 to 12, respectively.ConclusionOur study suggests, elderly males with visual symptoms, sight loss, lower CRP are a high-risk group with increased mortality within GCA. Difficult to treat disease is seen in half of all patients especially with LV involvement. This group responds well to early DMARD use achieving remission comparable to the remitting group at 12 months. Current therapies fail to achieve remission in 9.5 % of cases. HS and HC show significant improvement mirroring clinical outcomes during first 12 months of therapy.References[1]Sebastian A et al. BMC Rheum. 2020[2]Schafer VS et al. Rheumatology 2017[3]van der Geest KSM et al. ARD 2020Table 1.comparison between the DMARD-used group and only GC group in all the GCA completed the 12 months follow upPatients' characteristicsGCA with completed follow-up (n=73)GCA treated with DMARD=36GCA not treated with DMARD=37Age, median (range) years73.5 (60-89)76 (60-89)Sex, Females, n (%)23 (64)24 (65)US halo score (HS)/IMT median (range)Temporal artery HS11 (0-23)13 (1-22)Axillary artery HS12 (0-21)12 (0-18)Axillary artery IMT (mm)0.77 (0.33-2.6)0.82 (0.39-1.21)Total HS22.5 (2-41)21 (5-40)Clinical features, n (%)Temporal headache25(69)30 (81)Scalp tenderness17 (47)19 (51)Jaw & Tongue claudication22 (61)24 (65)Polymyalgic symptoms21 (58)13 (35)Constitutional symptoms21 (58)18 (49)Any visual disturbance15 (42)21 (57)Partial or complete vision loss8 (22)7 (19)History of PMR6 (17)3 (8)Exam findings, n (%)Temporal artery abnormality24 (67)30 (81)AION/ CRAO8 (22)6 (16)Ocular nerve palsy1 (3)3 (8)Lab markers at baseline, median (range)CRP mg/dL,72.2 (6.4-292)59 (6-206)ESR mm/hr67 (9-130)57 (2-120)GC treatment, median (range)GC starting dose, (baseline)45 (0-60)50 (0-60)GC dose at 12m,5 (0-25)2.5 (0-10)Cumulative GC dose at 12m4627.5 (2600-10260.5)4622.5 (944-10737.5)Remission with prednisolone dose ≤5 mg at 12m, n (%)32 (89)33 (89)Acknowledgements:NIL.Disclosure of InterestsBhaskar Dasgupta Consultant of: Roche, Chugai, Sanofi, Grant/research support from: Roche, Sanofi, AbbVie, and GlaxoSmithKline, Kornelis van der Geest Speakers bureau: Roche, Grant/research support from: AbbVie, Alessandro Tomelleri: None declared, Pierluigi Macchioni: None declared, Giulia Klinowski: None declared, Carlo Salvarani: None declared, Abdul Kayani: None declared, Mohammad Tariq: None declared, Diana Prieto-Peña: None declared, Edoardo Conticini: None declared, Muhammad Khurshid: None declared, Sue Inness: None declared, Jo Jackson: None declared, Alwin Sebastian: None declared.
ABSTRACT
Background: COVID-19 is characterized by a dysregulated inflammatory response associated with disease severity, poor prognosis and death. The aim of this study was to describe the real-life use of high-dose anakinra (ANK, a recombinant IL-1 receptor antagonist) among patients with COVID-19 who received remdesivir (REM). Methods: Cohort study including 277 patients with COVID-19 hospitalized at IRCCS San Raffaele Hospital between September 1st,2020 and February 28th, 2021;58 patients were treated with REM+ANK and 219 patients with REM only. ANK was administered intravenously at a dose of 5mg/kg every 12 hours. Patients were treated according to available local and international guidelines;corticosteroids and anticoagulation were administered when not contraindicated. Results are described by median (IQR) or frequency (%);P-values (P) were calculated by chi-square or Fishers' exact test and Wilcoxon rank-sum test, as appropriate. Survival estimates at 28 days were calculated using Kaplan-Meier curves. Results: At hospital admission (Table 1), patients treated with REM+ANK tended to be older [69 years (57-77) vs 62 years (53-75), P=0.06], had a significant lower PaO2/FiO2 [135 (91-220) vs 246 (172-299), P=0.0001], higher aspartate aminotransferase [51U/L (34-74) vs 40U/L (30-53), P=0.001], lactate dehydrogenase [405U/L (296-496) vs 334U/L (279-419), P=0.008], D-dimer [0.86mcg/mL (0.48-1.57) vs 0.67mcg/mL (0.39-1.17), P=0.048], ferritin [1167ng/mL (804-1983) vs 683ng/mL (391-1153), P<0.0001] and C-reactive protein [82mg/L (38-136) vs 58 mg/L (27-96), P=0.004), and were more frequently admitted to the Intensive Care Unit within the first 48 hours [3 (1.1%) vs 0, P=0.007). REM and ANK were started early within a median of 0 (0-2) and 1.5 days (0-3) since hospitalization, respectively. The Kaplan-Meier estimate of mortality at 28 days was 17.2% (95%CI 8.8-32.1%) in the REM+ANK group (8 deaths) and 21.4% (95%CI 13.3-33.3%) in the REM group (18 deaths;log-rank test P=0.797). Median time to death was 14 days (9-29) in the REM+ANK group vs 19 days (12-27) in the REM group (P=0.523). Conclusion: Real-life use of high-dose ANK in COVID-19 patients treated with REM was reserved for subjects with severe respiratory failure and a more pronounced inflammatory status. Nevertheless, mortality at 28 days was not significantly different among patients treated with or without ANK. Further analyses are warranted to verify the impact of ANK addition to REM in patients with a hyperinflammatory profile.
ABSTRACT
Background:Patients with severe COVID-19 pneumonia and hyperinflammation face increased mortality. There is an urgent need for effective treatments to reduce the burden of the COVID-19 pandemic.Objectives:Our protocol aimed at evaluating the potential improvement in clinical outcomes with mavrilimumab, an anti-Granulocyte/Macrophage Colony-Stimulating Factor Receptor alpha (GM-CSFRα) monoclonal antibody, in patients with COVID-19 pneumonia and systemic hyper-inflammation.Methods:Single-center, open-label, single active arm intervention;Adult patients with severe COVID-19 pneumonia (as evaluated by CT scanning), hypoxia (PaO2:FiO2 ratio ≤ 300 mmHg), and systemic hyper-inflammation (increased C-reactive protein [CRP] ≥ 100 mg/mL and/or ferritin ≥ 900 μg/L, increased lactate dehydrogenase [LDH]) received a single intravenous dose of mavrilimumab added to standard of care;follow-up 28 days. Main outcomes measure was time to clinical improvement (reduction ≥ 2 categories on the 7-point WHO clinical status scale, 1=discharge, 7=death);others included time to discharge from hospital;% of pts achieving a clinical improvement;survival;mechanical-ventilation free survival;time to fever resolution;CRP;PaO2:FiO2 ratio.Results:A mavrilimumab group (n=13 COVID-19 patients, non-mechanically ventilated, median age 57 [IQR, 52-58], males 12 [92%], febrile 11 [85%];PaO2:FiO2 195.5[166.7–215.0]) was compared to a cohort of 26 contemporaneous patients with similar baseline characteristics. Death occurred in 0% (n=0/13) of mavrilimumab recipients and 27% (n=7/26) of comparison-group patients (log rank p=0.046) during the 28-day follow-up. 100% (n=13) of mavrilimumab recipients and 65% (n=17) of comparison-group patients achieved clinical improvement (p=0.018) at Day 28, with earlier improvement (median 8.0 [IQR, 5.0–11.0] days vs 18.5 [11.0–NE] days) (p0.001) in mavrilimumab recipients. Fever had resolved in 91% (n=10/11 febrile patients) of mavrilimumab recipients by Day 14, compared to 61% (n=11/18 febrile) of patients in the comparison group (p=0.110);fever resolution was faster in mavrilimumab recipients versus controls (median 1.0 [IQR, 1.0–2.0] day vs 7.0 [3.0 - NE] days, respectively, p=0·009). Mavrilimumab was well tolerated in all patients.Conclusion:Patients with severe COVID-19 pneumonia and systemic hyper-inflammation who received treatment with mavrilimumab had better clinical outcomes compared to patients receiving routine care. Mavrilimumab was well-tolerated. Randomized controlled trials are warranted to confirm our findings.References:[1]Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62[2]Mehta P, McAuley DF, Brown M, et al. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-4Disclosure of Interests:Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Emanuel Della Torre: None declared, Piera Angelillo: None declared, Alessandro Tomelleri: None declared, nicola boffini: None declared, Stefano Tentori: None declared, Francesca Mette: None declared, Patrizia Rovere-Querini: None declared, Annalisa Ruggeri: None declared, Teresa D’Aliberti: None declared, Paolo Scarpelllini: None declared, Giovanni Landoni: None declared, Francesco De Cobelli: None declared, John F. Paolini Shareholder of: Kiniksa, Employee of: Kiniksa, Alberto Zangrillo: None declared, Moreno Tresoldi: None declared, Bruce C. Trapnell Consultant of: Kiniksa, Fabio Ciceri: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI