Use of Tocilizumab in hospitalized patients during the first wave of the COVID-19 pandemic

Introduction: The aim of this study was to characterize the use of tocilizumab in a hospital. Method: Retrospective cohort study including adult SARS-CoV-2 infected inpatients with moderately severe infection (PaO2/FiO2 < 300). ORs for mortality and treatment success were calculated. Results: The tocilizumab group (n=18), presented 5 days of symptoms vs 7 days in the untreated group (n=71). Minimum PaO2/FiO2 was 147.5 (95%CI: 116.7 to 194.0) vs 255.6 (95%CI: 320.7 to 452.4) (p=0.01).No significant differences were found between the two groups concerning survival (OR=1.22; 95%CI: 0.38 to 3.92), nor treatment success (OR=0.46; 95%CI: 0.16 to 1.33). After adjusting for age, sex and total corticosteroid dose, OR for success was 0.18 (95%CI: 0.03 to 0.96), while mortality was not significant. Conclusions: The use of tocilizumab in moderately severe hospitalized patients could decrease the hyperinflammatory state preventing disease progression (AU)

Introducción: El objetivo del estudio fue estudiar la utilización de tocilizumab en un centro hospitalarioMétodo:Estudio de cohortes retrospectivo que incluyó pacientes ingresados adultos infectados por SARS-CoV-2, con una infección de gravedad moderada (PaO2/FiO2 < 300). Se calcularon las OR de mortalidad y éxito del tratamiento. Resultados: El grupo tocilizumab (n=18), tuvo 5 vs 7 días con síntomas en el grupo no tratado (n=71). El PaO2/FiO2 mínimo fue de 147,5 (IC95%: 116,7 a 194,0) versus 255,6 (IC95%: 320,7 a 452,4) (p=0,01).No se encontraron diferencias significativas entre ambos grupos en supervivencia (OR=1,22; IC95%: 0,38 a 3,92); ni en el éxito del tratamiento (OR=0,46; IC95%: 0,16 a 1,33). Tras ajustar por edad, sexo y dosis total de corticoide, OR de éxitos fue 0,18 (IC95%: 0,03 a 0,96), mientras que mortalidad no fue significativa. Conclusiones: El uso de tocilizumab en pacientes hospitalizados moderadamente graves podría disminuir su estado hiperinflamatorio (AU)

HLA-B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.

OBJECTIVE: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. METHODS: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . RESULTS: The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. CONCLUSION: These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.