BackgroundThe anti–IL6 receptor-α antibody tocilizumab (TCZ) demonstrated numerical improvement in modified Rodnan skin score (mRSS) and clinically relevant preservation of lung function (LF) (assessed by forced vital capacity [FVC]) in systemic sclerosis (SSc) patients (pts) in a ph 2 trial.1 ObjectivesReport the efficacy and safety (sft) of TCZ vs placebo (PBO) in SSc pts from the double-blind period of ph 3 trial (NCT02453256).MethodsSSc pts were randomly assigned 1:1 to weekly subcutaneous TCZ 162 mg or PBO for 48 wks. Primary endpoint was mean difference (diff) in change (Δ) from baseline (BL) to wk 48 in mRSS for TCZ vs PBO. Key secondary endpoints were ΔBL%-predicted FVC (ppFVC) and time to Tx failure (time from first study treatment (Tx) to first occurrence of death, decline in FVC >10%, increase in mRSS >20% and mRSS ≥5, or occurrence of predefined SSc-related Cx). Chest high-resolution computed tomography (HRCT) and ACR Combined Response in SSc (CRISS) were exploratory endpoints.ResultsOf 106 PBO- and 104 TCZ-treated pts, 81% were women and 31% had previous or concurrent interstitial lung disease based on history. BL mean values were age 48 yrs, SSc duration 23 mts, mRSS 20.4, ppFVC 82.1%, and ppDLCO 75.6%. Mean BL computer-assisted quantitative lung fibrosis of the most affected lobe (QLF-LM) was 4.7% for the PBO group and 5.5% for the TCZ group. At wk 48, the primary endpoint was not significant (ΔBL mRSS: PBO, −4.4; TCZ, −6.1; adjusted least squares mean diff, −1.7 [95% CI: −3.8, 0.3]; p=0.098) (Fig 1A). All p values for other endpoints were nominal. The cumulative distribution of wk 48 ΔBL ppFVC favored TCZ over PBO (median [IQR]: PBO, −3.9 [−7.2, 0.6] vs TCZ, −0.6 [−5.3, 3.9]; van Elteren nominal p=0.0015). The diff in mean ΔBL FVC at wk 48 between Tx groups was 167 mL (95% CI: 83, 250), favoring TCZ (Fig 1B). At wk 48, 5 (5.4%) TCZ-treated pts experienced ≥10% absolute decline in ppFVC compared with 15 (16.5%) for PBO. The HR (95% CI) for time to Tx failure was 0.6 (0.4, 1.1), numerically favoring TCZ (Cox proportional hazards model; p=0.082). ACR CRISS scores favored TCZ over PBO at wk 48: median (IQR), 0.89 (0.09-1.00) vs 0.25 (0.00-0.99) (p=0.023). HRCT showed less progression of lung fibrosis for TCZ than for PBO, which supports the FVC results. Sft results were consistent with Cx of SSc and the established TCZ sft profile; SAEs were reported by 17% of PBO pts and 13% of TCZ pts; serious infections were reported by 7% and 2% of pts, respectively.ConclusionThe primary mRSS endpoint was not met; however, TCZ Tx resulted in clinically relevant differences in FVC with preservation of LFS and improvement in fibrosis, measured by HRCT, in SSc pts.Disclosure of Interests: Dinesh Khanna Shareholder of: Eicos Sciences, Inc, Grant/research support from: Bayer, BMS, Pfizer, Horizon, Consultant for: Actelion Acceleron, Arena, Bayer, BI, BMS, CSL Behring, Corbus, Cytori, GSK, Genentech/Roche, Galapagos, Employee of: Elcos Sciences, Inc, Celia J. F. Lin Shareholder of: Genentech, Employee of: Genentech, Jona...

No abstract

Background:As of the 25th of January 2021, more than 150 thousand deaths as consequence of COVID-19 have been reported in Mexico [1]. Advanced age, male gender and comorbidities have been described as risk factors for severe disease and mortality in general population [2]. COVID-19 mortality in Mexican patients with rheumatic and musculoskeletal diseases (RMDs) is unknown.Objectives:To describe characteristics of Mexican patients with RMDs and COVID-19, and to analyse factors associated with mortality.Methods:The Global Rheumatology Alliance COVID-19 (GRA) physician reported registry, is an international effort to collect information on COVID19 in adult patients with RMDs. GRA is an observational registry. The first patient from Mexico was registered on April 17, 2020. All Mexican patients registered in GRA until October 30, 2020 were included in this analysis. The association of mortality with demographic and clinical variables was estimated using logistic regression analysis.Results:A total of 323 patients were registered, with a median age of 52 (IQR 41-61) years old, 166 (51.4%) patients lived in Mexico City. The most frequent RMDs were rheumatoid arthritis, 149 (46.1%) and systemic lupus erythematosus, 24 (19.8%). Over a third of patients with RMDs and COVID-19 (119 (36.8%)) were hospitalized, and 43 (13.3%) died. Table 1 shows clinical and demographic characteristics. In the univariable analysis, the absence of comorbidities was a protective factor, OR 0.3 (95% CI 0.1-0.6). Factors associated with mortality at COVID-19 diagnosis were age over 65 years old, having type 2 diabetes, chronic renal insufficiency, treatment at COVID-19 diagnosis with corticosteroids or with CD20 inhibitors. In the multivariable adjusted analysis, these factors remained independently associated with mortality. No associations with other treatments or comorbidities at COVID-19 diagnosis were found.Conclusion:Mexican patients with RMDs and COVID-19 in the GRA physician reported registry had a mortality of 13.3%. Factors associated with mortality were those described in the general population, such as older age and being on corticosteroids and CD20 inhibitors treatment at COVID-19 diagnosis.References:[1]WHO. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. (accessed 26 January, 2021).[2]Zhou F, et al. Lancet 2020;395(10229):1054-62.Table 1.Clinical and demographic characteristics of patients with rheumatic diseases and COVID-19 in Mexico and mortality.Characteristics at COVID-19 diagnosisTotalN=323Death43 (13.3)Survivors280 (86.7)UnivariableOR (95% CI)MultivariableOR (95% CI)Women, n(%)268 (82.9)33 (76.7)235 (83.9)0.6 (0.3-1.4)0.5 (0.2-1.3)Age >65 years old, n(%)62 (19.2)18 (41.9)44 (15.7)3.9 (1.9-7.7)3.9 (1.9-8.3)RMDs* n(%)-Rheumatoid arthritis149 (46.1)23 (53.5)126 (45.0)1.6 (0.7-3.7)-Systemic Lupus Erythemathosus64 (19.8)10 (23.3)54 (19.3)1.6 (0.6-4.3)-Spondyloarthritis (axial and others)33 (10.2)2 (4.7)31 (11.1)0.1 (0.1-2.8)-Others77 (23.8)8 (18.6)69 (24.6)1-Moderate/High disease activity1, n(%)57 (18.6)7 (17.9)50 (18.7)1.0 (0.4-2.5)-None comorbidities, n(%)136 (42.1)8 (18.6)128 (45.7)0.3 (0.1-0.6)-Hypertension*, n(%)88 (27.2)12 (27.9)76 (27.1)1.0 (0.5-2.1)-Type 2 Diabetes*, n(%)49 (15.2)13 (30.2)36 (12.9)2.9 (1.4-6.1)2.4 (1.1-5.4)Obesity*, n(%)21 (6.5)3 (6.9)18 (6.4)1.1 (0.3-3.9)-Chronic obstructive pulmonary disease*, n(%)15 (4.6)1 (2.3)14 (5.0)0.5 (0.1-3.5)-Chronic renal insufficiency*, n(%)17 (5.2)6 (13.9)11 (3.9)3.9 (1.4-11.4)3.4 (1.1-10.4)Cardiovascular diseases*, n(%)14 (4.3)2 (4.7)12 (4.3)1.1 (0.2-5.0)-Corticosteroids*, n(%)171 (52.9)30 (69.7)141 (50.3)2.3 (1.1-4.5)3.0 (1.4-6.5)CsDMARD*, n(%)247 (76.5)33 (16.3)214 (76.4)1.0 (0.5- 2.2)-CD20 inhibitor*, n(%)21 (6.5)7 (16.3)14 (5.0)3.7 (1.4-9.9)4.9 (1.7-14.5)*Overlapped, 1 307 patients.Disclosure of Interests:None declared

Background:COVID-19 outcomes in Mexican patients with rheumatic diseases (RDs) in comparison to general population patients are unknown.Objectives:To compare mortality and hospitalization of COVID-19 patients with RDs and those without.Methods:We included for this study all the Mexican patients with RDs and COVID-19 registered from April 17th to October 30th, 2020 in the COVID-19 Global Rheumatology Alliance registry. We compare clinical and demographic characteristics of patients with RDs and COVID-19 to patients with COVID-19 that were selected randomly from the Mexican Epidemiology database (1:3). A logistic regression analysis was performed to adjust for confusion variables.Results:We included 322 patients with COVID-19 and RDs and 969 controls without RDs. Table 1 shows the demographic characteristics and comorbidities of both groups. Bivariate analysis showed that patients with RDs had higher mortality, were older, and were more frequently hospitalized. Comorbidities, such as diabetes, hypertension, cardiovascular and renal diseases were also more frequent in patients with RDs. In the multivariate analysis, having a RD was no longer associated with mortality (Figure 1).Figure 1.Multivariate analysis of mortalityConclusion:Patients with RDs had higher comorbidities, hospitalizations, and mortality than the general population in the bivariate analysis. However, adjusted multivariate analysis showed that the odds for mortality were not increased because of having a RD. These findings suggest that the increased mortality of Mexican patients with RDs may be explained by the higher frequency of comorbidities in this population.Table 1.Comparison of patients with COVID-19 with and without RDsCOVID-19 patients without RDsCOVID-19 patients with RDsp-valueN969323Age (mean (SD))42.6 (17.4)51.2 (13.9)<0.001Sex = Male (%)455 (47.0)55 (17.0)<0.001Deceased = Yes (%)55 (5.7)43 (13.3)<0.001Hospitalization = Hospitalized (%)164 (16.9)152 (47.1)<0.001Intubation = Yes (%)27 (2.8)32 (11.8)<0.001COPD_Asthma = Yes (%)37 (3.8)15 (4.6)0.522Diabetes = Yes (%)114 (11.8)49 (15.2)0.116Obesity = Yes (%)128 (13.3)21 (6.5)0.001Hypertension = Yes (%)152 (15.8)88 (27.2)<0.001Cardiovascular disease = Yes (%)19 (2.0)14 (4.3)0.02CRF = Yes (%)22 (2.3)17 (5.3)0.007Pregnancy = Yes (%)5 (0.5)2 (0.6)0.827Smoker = Yes (%)86 (8.9)10 (3.1)0.001Abbreviations: RDs, rheumatic diseases; COPD, chronic obstructive pulmonary disease; CRF, chronic renal failure.Disclosure of Interests:None declared

BackgroundPatients with immune-mediated rheumatic diseases (IRD) have poorer outcomes of SARS-CoV-2 infection compared to the general population.ObjectivesTo assess and compare clinical course, severity and complications of SARS-CoV-2 infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Mexico and Argentina.MethodsData from both national registries, CMR-COVID (Mexico) and SAR-COVID (Argentina), were combined. Briefly, adult IRD patients with SARS-CoV-2 infection were recruited between 08.2020 and 09.2022 in SAR-COVID and between 04.2020 and 06.2022 in CMR-COVID. Sociodemographic data, comorbidities, and DMARDs were recorded, as well as clinical characteristics, complications, and treatment for SARS-CoV-2 infection. Descriptive analysis. Chi square, Fisher, Student T, Mann Whitney U tests and multiple logistic regression analyses were performed.ResultsA total of 3709 patients were included, 1167 (31.5%) from the CMR-COVID registry and 2542 (68.5%) from the SAR-COVID registry. The majority (82.3%) were women, with a mean age of 50.4 years (SD 14.4). The most frequent IRD were rheumatoid arthritis (47.5%) and systemic lupus erythematosus (18.9%). Mexican patients were significantly older, had a higher female predominance and had higher prevalence of rheumatoid arthritis, antiphospholipid syndrome, and axial spondyloarthritis, while the Argentine patients had more frequently psoriatic arthritis and ANCA-associated vasculitis. In both cohorts, approximately 80% were in remission or low disease activity at the time of infection. Mexicans took glucocorticoids (43% vs 37%, p<0.001) and rituximab (6% vs 3%, p<0.001) more frequently. They also reported more comorbidities (48% vs 43%, p=0.012).More than 90% of patients presented symptoms related to SARS-CoV-2 infection. The frequency of hospitalization was comparable between the groups (23.4%), however, the Mexicans had more severe disease (Figure 1) and a higher mortality rate (9.4% vs 4.0%, p<0.0001). After adjusting for risk factors, Mexicans were more likely to die due to COVID-19 (OR 2.2, 95%CI 1.5-3.1).ConclusionIn this cohort of patients with IRD from Mexico and Argentina with SARS-CoV-2 infection, the majority presented symptoms, a quarter were hospitalized and 6% died due to COVID-19. Mexicans presented more severe disease, and after considering risk factors they were two times more likely to die.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsCarolina Ayelen Isnardi Grant/research support from: SAR-COVID is a multi- sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or infuenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database, Deshire Alpizar-Rodriguez: None declared, Marco Ulises Martínez-Martínez: None declared, Rosana Quintana: None declared, Ingrid Eleonora Petkovic: None declared, Sofia Ornella: None declared, Vanessa Viviana Castro Coello: None declared, Edson Velozo: None declared, David Zelaya: None declared, María Severina: None declared, Adriana Karina Cogo: None declared, Romina Nieto: None declared, Dora Aida Pereira: None declared, Iris Jazmin Colunga-Pedraza: None declared, Fedra Irazoque-Palazuelos: None declared, GRETA CRISTINA REYES CORDERO: None declared, Tatiana Sofía Rodriguez-Reyne: None declared, JOSE ANTONIO VELOZ ARANDA: None declared, Cassandra Michele Skinner Taylor: None declared, INGRID MARIBEL JUAREZ MORA: None declared, Beatriz Elena Zazueta Montiel: None declared, Atzintli Martínez: None declared, Cesar Francisco Pacheco Tena: None declared, Guillermo Pons-Estel: None declared.