Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
BackgroundThe safety profile of a-TNF drugs might have regional differences due to socio economic factors and epidemiology of infectious diseases. In 2009, the Brazilian Society of Rheumatology started BiobadaBrasil registry, part of a Latin America project (BiobadaAmerica) with methodological support of SER and BiobadaserObjectivesTo report the incidence of adverse events (AE) in patients exposed to a-TNF drugs in BrazilMethodsSince 2009, 31 centers from 21/26 states included patients with active rheumatic diseases starting a biologic drug or a synthetic DMARD (control group). A constant monitoring of data quality has been done (online, by phone and ïn situ”). This study focuses on serious AE (SAE) and serious infectious AE (SIAE) in patients with RA and SpA (AS and PsA) exposed to a-TNF.Time of exposure was set from start of the drug to the date of last administration plus twice the half-life. Continuous variables were expressed as mean (SD).AE incidence rate as 1000 p/y with 95%CI.Data 31/12/13Results1483 subjects with RA (952) and SpA (531) exposed to a-TNF drugs were included in BiobadaBrasil, 3882 p/y, mean age 47 (12) yrs, mean dis dur 9 (8) yrs, 65% females. Controls were 529 (RA 491, SpA 38), 1607 p/y, mean age 50 (12) yrs, mean dis dur 6 (8) yrs, 82% females. The incidence rates of AE in the a-TNF vs control groups were: SAE 69 [61,78] vs 30 [23,40] (ratio 2.31 [1.7,3.14] p=0.000), SIAE 35 [30,41] vs 12 [8,19] (ratio 2.96 [1.83,4.79] p=0.000). First a-TNF was associated with lower incidence of SAE and SIAE when compared with the subsequent (SAE 66 vs 97, ratio 1.47 [1.05,2.06], p=0.024) (SIAE 34 vs 44, ratio 1.22 [0.78,2.10], p=0.3). SAE and SIAE were less frequent in SpA than in RA (SAE ratio 0.69 [0.52,0.93], p=0.014) (SIAE ratio 0.53 [0.33,0.83], p=0.006)ConclusionsIn BiobadaBrasil registry, patients exposed to a-TNF drugs have incidence rates of SAE and SIAE respectively 2 and 3-fold those of the control group, significantly lower in SpA than in RA.AcknowledgementsBiobadaBrasil study group: P Cabral data quality control, BSR, A Kakehasi UFMG Belo Horizonte, A. Ximenes HGG, Goiania, F Sztajnbok UERJ Rio Janeiro, H. Pereira HUGV Manaus, I Silveira PUCRS Porto Alegre, A Ranzolin UFPE Recife, A Hayata CRO Osasco, M Abreu UFSC São Carlos, M Scheinberg HAS São Paulo, W Bianchi SCM Rio Janeiro, W Chahade HSPE São PauloDisclosure of InterestNone declared
Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged.For clarity, all collaborators are listed in this correction article.
IntroductionThe detection of leprosy in children is an important epidemiological marker of the disease, indicating the community’s early exposure to Mycobacterium leprae and active transmission of the infection.MethodsIn order to detect new cases among children by combining clinical evaluation and laboratory tests, we conducted an active case finding among individuals under 15 years old on Caratateua Island, located in the city of Belém, in the Pará state, an endemic region in the Amazon. Dermato-neurological examination, collection of 5 mL of peripheral blood for IgM anti-PGL-I antibody titration, and intradermal scraping for bacilloscopy and amplification of the specific RLEP region by qPCR were performed.ResultsOut of the 56 examined children, 28/56 (50%) new cases were identified. At the time of evaluation, 38/56 (67.8%) children presented one or more clinical alterations. Seropositivity was detected in 7/27 (25.9%) new cases and 5/24 (20.8%) undiagnosed children. DNA amplification of Mycobacterium leprae was observed in 23/28 (82.1%) of new cases and in 5/26 (19.2%) of non-cases. Out of the total cases, 11/28 (39.2%) were exclusively diagnosed by clinical evaluation performed during the active case finding. Seventeen new cases (60.8%) were detected considering the clinical alterations found in addition to positive results for qPCR. In this group, 3/17 (17.6%) qPCR-positive children presented significant clinical changes 5.5 months after the first evaluation.DiscussionOur research detected a number of cases 5.6 times higher compared to the total number of pediatric cases recorded throughout the year 2021 in the municipality of Belém, which shows a critical scenario of underdiagnosing of leprosy among children under 15 years old in the region. We propose the use of qPCR technique to identify new cases among children with oligosymptomatic or early disease in endemic areas, in addition to the training of Primary Health Care professionals and the implementation of the Family Health Strategy coverage in the visited area.
Background Treatment survival of biological agents can be influenced by many factores. It seems to be different between different rheumatic disease. Objectives To compare the biological treatment survival of the different rheumatic disease to analyze the main causes of treatment discontinuation in patients with rheumatoid arthritis (RA) from the Brazilian Registry – BIOBADABRASIL. Methods Cohort from Brazilian Society Registry of Biological Therapy in Rheumatic Diseases (BIOBADABRASIL)including 2191 patients, including 1266 (57%) rheumatoid arthritis (RA), 678 (29.5%) spondyloarthritis 247 (12.5%) with others rheumatic disease in use of their first biological agent. They were analyzed at baseline up to 4 years(2008-2012). Sex, age, disease duration, co-morbidities and concomitant treatments at baseline were recorded. Kaplan-Meier estimates, Chi-square, Kruskal-Wallis and Wilcoxon-Mann-Whitney tests, Cox regression analysis were applied when appropriate. Results Of the 2191 studied patients, 65,7% were women, 47,98 ± 13,85 yrs, 47,98 ± 13,85 months of disease duration; 9.5% were smokers; 6.8% had diabetes, 7.8% had hypercholesterolemia. DMARDs at baseline were observed in 77.9% of the patients, 63.9% received methotrexate, 57%, steroids. Regarding biological agents 44.7% (N=979) received infliximab (IFX), 25.7% (N=562) adalimumab (ADA), 21% (N= 460) etanercept (ETA), 4,1% (N=90) rituximabe (RTX), 2.5% (N=55) tocilizumab (TCZ), 2.1% (N= 45) abatacept (ABA). Retention rate of biological agents was 72.7% of total sample and 72% for patients receiving anti TNF agentes. Survival treatment for Spondyloarthritis patients (41.45 ± 0.5; CI= 40.34 – 42.57) was higher (p≤ 0,001) compared to RA (37.45 ± 0.46; CI= 36.47 – 38.44) or to other rheumatic disease (39.58 ± 0.98; CI= 37.49 – 41.66). The main cause of disruption was inefficacy (N=277; 46,1%) followed by adverse events (N= 225; 37.4%) and others (N= 99; 16.5%). Conclusions Results showed a good anti-TNF survival since 70% continued treatment. Despite being a developing country, the primary cause of interruption was inefficacy and not adverse events. Patients with spondyloarthritis showed better survival for biological therapy. Acknowledgements Biobadaser; Others Biobadabrasil investigators (Fabiana Britto Goulart, Luís Sérgio Guedes Barbosa, Willian Chahade, Antonio Carlos Ximenes, Marcelo Pinheiro, Mailze Campos Bezerra, José Eduardo Martinez, Mária Fátima Lobato Sauma, Flávio Sztajnbok, Gláucio r. Werner de Castro, Nilzio Antonio da Silvaa, Adriana Maria Kakehasi, Helena Lúcia Alves Pereira, Márcia Bandeira, Mário Newton Azevedo, Cristina Ellert Salomão, Cesar Baaklini, Walber Vieira). Disclosure of Interest None Declared
BackgroundThe safety profile of biologic drugs might have substantial regional differences. Since 2009, the Brazilian Society of Rheumatology runs BiobadaBrasil, a registry for monitoring of biologic therapies in rheumatic diseases, in collaboration with other Latin America countries (BiobadaAmerica) and with BiobadaserObjectivesTo report the incidence of serious adverse events (SAE) in Rheumatoid Arthritis (RA) patients exposed to biologic drugs in BrazilMethodsBiobadaBrasil counts on thirty two centers, from almost all Brazilian states, that prospectively include patients with active rheumatic diseases who started a biologic drug or a synthetic DMARD as a parallel control group. A constant three level monitory of data quality is maintained (online, by phone and “in situ”). This study focuses on SAE (for definition: Protocolo 1.1 at ) in RA patients exposed to biologics from January 2009 to June 2015. Time of exposure was set from start of the drug to the date of last administration or censorship. Continuous variables were expressed as mean with standard deviation (SD). SAE incidence rate was calculated per 1000 patient/years with 95%CIResultsOut of a total of 1649 subjects with RA, 1121 were exposed to biologics (4735 p/y), 91% a-TNFs, follow-up 2.8 (2.2) yrs, 85% females, at baseline: age 50 (14) yrs, disease duration 9 (8) yrs, DAS28 5.4 (1.4). Controls were 528 (1971 p/y), follow-up 3.6 (2.2) yrs, 86% females, at baseline: age 54 (13) yrs, disease duration 6 (8) yrs, DAS28 5.1 (3.1). The incidence rates of SAE in the biologics and control groups were 86 [78, 94] vs 34 [27, 44] (ratio 2.5 [1.9, 3.3], p<0.001). There was no statistical difference in SAE incidence between a-TNFs and non-a-TNF biologics. Among a-TNFs, Adalimumab was associated with less SAE (64 [53,79]) compared with Etanercept (93 [77,113] p<0.01) and Infliximab (102 [86,122] p=0.0003). SAE were more frequent with subsequent a-TNF than with the first, 107 [87, 132] vs 79 [70, 90] (ratio 1.4 [1.1, 1.7] p=0.0078). Among SAEs with biologics, serious infections account for half of the events (43 [37–49])ConclusionsIn the BiobadaBrasil registry the incidence of SAE is 2 fold higher with biologics than with synthetic DMARDs, and higher with subsequent a-TNF than with the firstAcknowledgementfor data monitoring P Cabral, for contributing to BiobadaBrasil registry, L.Barbosa, W.Chahade, A.Hayata, A.Kakehasi, M.Pinheiro, A.Ranzolin, M.Scheinberg, F.Sztajnbok, I.SilveiraDisclosure of InterestNone declared
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