EDUARDO FERREIRA BORBA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- 2019-EULAR/ACR classification criteria domains at diagnosis: predictive factors of long-term damage in systemic lupus erythematosus(2022) INSFRAN, Carlos E.; AIKAWA, Nadia E.; PASOTO, Sandra G.; FILHO, Dilson M. N.; FORMIGA, Francisco F. C.; PITTA, Ana C.; BORBA, Eduardo F.; RIBEIRO, Carolina T.; SILVA, Clovis A.; BONFA, EloisaThe objective of this study is to assess the role of the 2019-European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria at diagnosis and its domains in predicting long-term damage in systemic lupus erythematosus(SLE). We performed a retrospective analysis using an electronic chart database utilized in routine clinical care of SLE patients and established in 2000 in a tertiary hospital. Two hundred and nine consecutive SLE patients with disease onset >= 18 years old and long disease duration were included. Cumulative damage at the last visit was scored using the SLICC/ACR-Damage Index (SDI). The median age at SLE diagnosis was 28 years (18-63), disease duration was 14 years (8-25), and 88% were females. Damage (SDI >= 1) was observed in 116/209 (55%). Patients with (SDI >= 1, n=116) and without damage (SDI=0, n=93) had similar median disease duration [14 (8-25) vs. 12 (8-25) years, p=0.090[ and age at diagnosis [23 (18-55) vs. 23 (18-56) years, p=0.998[. No correlation was observed between total 2019-EULAR/ACR score at diagnosis and SDI at last visit (r=0.007, p=0.913). Presence of renal domain at diagnosis was associated with renal damage at last visit (OR=3.6, 95%CI 1.2-10.4, p=0.017) and antiphospholipid antibodies domain predicted neuropsychiatric damage (OR=3.0, 95%CI 1.2-7.6, p=0.015). A ROC analysis identified that a cut-off >24 in 2019-EULAR/ACR score could predict a trend for renal damage (p=0.077) with a lower renal survival (Kaplan-Meier curve) for patients above this limit (p=0.029). A multivariate logistic regression analysis revealed that 2019-EULAR/ACR score >24 at diagnosis (OR 4.583, 95%CI 1.052-19.962, p=0.043) was independently associated with renal damage. Specific domains in the 2019-EULAR/ACR criteria at diagnosis were associated with long-term organspecific damage, particularly renal and neuropsychiatric harm. A 2019-EULAR/ACR score >24 predicted worse renal survival.
- Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases(2022) AIKAWA, Nadia Emi; BALBI, Verena Andrade; BORBA, Eduardo Ferreira; TONACIO, Adriana Coracini; SALLUM, Adriana Maluf Elias; CAMPOS, Lucia Maria Arruda; KOZU, Katia Tomie; VENDRAMINI, Margarete Borges; FONTOURA, Nicole; AZEVEDO, Adriana de Souza; SCHWARCZ, Waleska Dias; SARTORI, Ana Marli Christovam; ANTONANGELO, Leila; SILVA, Clovis Artur; BONFA, EloisaYellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (similar to 5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293; p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas. (C) 2021 The Authors.
- Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients(2022) SILVA, Clovis A.; MEDEIROS-RIBEIRO, Ana C.; KUPA, Leonard V. K.; YUKI, Emily F. N.; PASOTO, Sandra G.; SAAD, Carla G. S.; FUSCO, Solange R. G.; PEREIRA, Rosa M. R.; SHINJO, Samuel K.; HALPERN, Ari S. R.; BORBA, Eduardo F.; SOUZA, Fernando H. C.; GUEDES, Lissiane K. N.; MIOSSI, Renata; BONFIGLIOLI, Karina R.; DOMICIANO, Diogo S.; SHIMABUCO, Andrea Y.; ANDRADE, Danieli C. O.; SEGURO, Luciana P. C.; FULLER, Ricardo; SAMPAIO-BARROS, Percival D.; ASSAD, Ana P. L.; MORAES, Julio C. B.; GOLDENSTEIN-SCHAINBERG, Claudia; GIARDINI, Henrique A. M.; SILVA, Henrique C.; MARTINS, Victor A. O.; VILLAMARIN, Lorena E. B.; NOVELLINO, Renata S.; SALES, Lucas P.; ARAUJO, Carlo S. R.; SILVA, Matheus S. R.; FILHO, Dilson M. N.; LOPES, Marta H.; DUARTE, Alberto J. S.; KALLAS, Esper G.; AIKAWA, Nadia E.; BONFA, EloisaCharacterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease. The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2(nd) dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).
- Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome(2022) SIGNORELLI, Flavio; BALBI, Gustavo Guimaraes Moreira; AIKAWA, Nadia E.; SILVA, Clovis A.; KUPA, Leonard de Vinci Kanda; MEDEIROS-RIBEIRO, Ana C.; YUKI, Emily F. N.; PASOTO, Sandra G.; SAAD, Carla G. S.; BORBA, Eduardo F.; SEGURO, Luciana Parente Costa; PEDROSA, Tatiana; OLIVEIRA, Vitor Antonio de Angeli; COSTA, Ana Luisa Cerqueira de Sant'Ana; RIBEIRO, Carolina T.; SANTOS, Roseli Eliana Beseggio; ANDRADE, Danieli Castro Oliveira; BONFA, EloisaObjective Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. Methods This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naive participants. Safety and aPL production were also assessed. Results We included 44 PAPS patients (31 naive) and 132 CG (108 naive) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (a beta 2GPI) IgG (p=0.513) and IgM (p=0.468). Conclusion We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.
article 3 Citação(ões) na Scopus Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort(2022) PINHEIRO, M. M.; PILEGGI, G. S.; KAKEHASI, A. M.; REIS, A. P. M. Gomides; REIS-NETO, E. T.; ABREU, M. M.; ALBUQUERQUE, C. P.; ARAUJO, N. C.; BACCHIEGA, A. B.; BIANCHI, D. V.; BICA, B.; BONFA, E.; BORBA, E. F.; BRITO, D. C. S. Egypto; CALDERARO, D. C.; DUARTE, A. L. B. Pinto; SANTO, R. O. Espirito; FERNANDES, P. R.; GUIMARAES, M. P.; GOMES, K. W. Poti; ILANA, G. G. Faustino; KLUMB, E. M.; MARQUES, C. D. L.; MELO, A. K. Guedes de; MONTICIELO, O. A.; MOTA, L. M. H.; MUNHOZ, G. A.; PAIVA, E. S.; PEREIRA, H. L. A.; PROVENZA, J. R.; RIBEIRO, S. L. E.; JR, L. F. Rocha; SATO, E. I.; SKARE, T.; SOUZA, V. A. de; VALIM, V.; LACERDA, M. V. G.; XAVIER, R. M.; FERREIRA, G. A.Objective To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC).Methods This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe.Results A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively).Conclusion Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.conferenceObject Latin-American Systemic Lupus Erythematosus Clusters(2022) QUINTANA, Rosana; NIETO, Romina; SCOLNIK, Marina; MERAS, Nidia; OTADUY, Cintia; SATTLER, Maria Emilia; LUCERO, Luciana Gonzalez; PEREZ, Nicolas; SILVA, Ana; MONTICIELO, Odirlei; DUARTE, Angela Luzia B.; NETO, Edgard Reis; MIMICA, Milena; MARTINEZ, Gustavo Aroca; QUINTANA-LOPEZ, Gerardo; ALVAREZ, Mario Moreno; SALINAS, Miguel Angel Saavedra; PORTELA, Margarita; SILVEIRA, Luis H.; VALLADARES, Ignacio Garcia; ABUD-MENDOZA, Carlos; ESQUIVEL-VALERIO, Jorge; DUARTE, Maria; LOUIS, Roberto Munoz; JUAREZ, Vicente; BORBA NETO, Eduardo Ferreira; CATOGGIO, Luis; ALARCON, Graciela; PUERTA, Jose; HARVEY, Guillermina; NOVATI, Elisa; ARTURI, Valeria; GRAGEDA, Wilfredo; PISONI, Cecilia; RIOBEIRO, Francinne Machado; YUKI, Emily Figueiredo Neves; HERRERA, Iris Guerra; TOBON, Gabriel; BONFANTI, Andres Cadena; FRAGOSO-LOYO, Hilda; MARTINEZ, Marie Teresa de; TRUJILLO, Claudia Selene Mora; UGARTE-GIL, Manuel; FLORES, Ernesto Zavala; ROBAINA, Ricardo; SILVEIRA, Gonzalo; ZAZZETTI, Federico; ORILLION, Ashley; PONS-ESTEL, Guillermo; PONS-ESTEL, Bernardo; SBARIGIA, Urbano- Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease(2022) LANG, Maria G.; VINAGRE, Carmen G. C.; BONFA, Eloisa; FREITAS, Fatima R.; PASOTO, Sandra G.; BRITO, Tatiane S.; SEGURO, Luciana P. C.; MARANHAO, Raul C.; BORBA, Eduardo F.Introduction The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking. Objective To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. Methods Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (C-14-Phospolipid, H-3-Cholesteryl ester, H-3-Triglyceride, and C-14-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. Results Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 +/- 14.04 vs 49.79 +/- 8.0 mg/dL; p < .05) but lower than CONTROL (58.37 +/- 14.04 vs 68.58 +/- 9.99 mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 +/- 16.43 vs 167.11 +/- 30.18 mg/dL; p < .05, 75.05 +/- 22.52 vs 96.05 +/- 25.63 mg/dL; p < .05) and CONTROL (148.16 +/- 16.43 vs 174.11 +/- 23.70 mg/dL; p < .05, 75.05 +/- 22.52 vs 88.53 +/- 20.24 mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 +/- 1.05% vs. 4.44 +/- 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 +/- 1.05% vs. 5.99 +/- 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 +/- 0.69% vs. 4.50 +/- 0.69% vs. 5.14 +/- 1.01%; p = .054), esterified cholesterol (5.24 +/- 0.70% vs. 4.96 +/- 0.89% vs. 5.69 +/- 1.27%; p = .079), and phospholipid (15.67 +/- 1.03% vs. 15.34 +/- 1.44% vs. 16.47 +/- 1.89%; p = .066) were similar among groups. Conclusion The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.
conferenceObject Patient-reported Outcomes in Lupus Low Disease Activity State: Impact of Fatigue(2022) RODRIGUES, Rodrigo De Moura; SANTOS, Alexandre Moura dos; CARDOSO, Daniel Sampaio; YUKI, Emily Figueiredo Neves; ANDRADE, Danieli Castro Oliveira de; PASOTO, Sandra Gofinet; BORBA NETO, Eduardo Ferreira; BONFA, Eloisa Silva Dutra de Oliveira; SEGURO, LucianaconferenceObject Baseline Characteristics of a Longitudinal, Multinational, Multiethnic Study of Lupus Patients, with or Without Lupus Nephritis(2022) NIETO, Romina; QUINTANA, Rosana; BORBA, Eduardo; HERNANDEZ, Lucia; FERNANDEZ-AVILA, Diana; MAURELLI, Laura; ALBA, Paul; BORDON, Florencia; ARIZPE, Fernando; BERBOTTA, Guillermo; SERRANO-MORALES, Rosa; BERTOLACCINI, Maria Constanza; KERZBERG, Eduardo; GARGIULO, Maria Angeles; RODRIGUEZ, Anabella; BARBOSA, Vitalina; GASPARIN, Andres; CAVALCANTI, Fernando; ALVINO, Laissa Alves; SEGURO, Luciana Parente Costa; MARTINS, Lucas Victoria de Oliveira; NIERA, Oscar; MASSARDO, Loreto; MARTINEZ, Gustavo Aroca; ARISTIZABAL, Ivana Nieto; PATARROYO, Paul Mendez; GAMARRA, Antonio Iglesias; VERA, Andres Zuniga; VERA-LASTRA, Olga-Lidia; CRISTOBAL, Mario Perez; MARTIN-NARES, Eduardo; AMEZCUA-GUERRA, Luis M.; GONZALEZ-BELLO, Yelitza; ENRIQUEZ, Octavio Gonzalez; GALARZO-DELGADO, Dionico; VAZQUEZ, Carolina; BARRIOS, Marcelo; LINARES, Magaly Alba; REATEGUI, Cristina; QUIROZ-ALVA, Ana; MORA, Teresandris Polanco; PIZZAROSSA, Carina; REBELLA, Martin; CRESPO, Maria; DANZA, Alvaro; BONFA, Eloisa Silva Dutra de Oliveira; ALARCON, Graciela; ZAZZETTI, Federico; ORILLION, Ashley; PONS-ESTEL, Guillermo; SBARIGIA, Urbano- Impact of Distinct Therapies on Antibody Response to SARS-CoV-2 Vaccine in Systemic Lupus Erythematosus(2022) YUKI, Emily F. N.; BORBA, Eduardo F.; PASOTO, Sandra G.; SEGURO, Luciana P.; LOPES, Michelle; SAAD, Carla G. S.; MEDEIROS-RIBEIRO, Ana Cristina; SILVA, Clovis A.; ANDRADE, Danieli C. O. de; KUPA, Leonard de Vinci K.; BETANCOURT, Lorena; BERTOGLIO, Isabela; VALIM, Juliana; HOFF, Camilla; FORMIGA, Francisco F. C.; PEDROSA, Tatiana; KALLAS, Esper G.; AIKAWA, Nadia E.; BONFA, EloisaObjective To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS-CoV-2 vaccine (Sinovac-CoronaVac) and the influence of different medications in SLE. Safety was also assessed. Methods We conducted a prospective controlled study of 232 SARS-CoV-2-naive SLE patients and 58 SARS-CoV-2-naive controls who were vaccinated with 2 doses of Sinovac-CoronaVac with a 28-day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed. Results Patients and controls were well balanced for age (P = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P < 0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108-0.427], P < 0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107-0.378], P < 0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC (P = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC (P < 0.001) and NAb positivity (P < 0.001). Safety analysis revealed no moderate/severe adverse events. Conclusion Sinovac-CoronaVac has a moderate immunogenicity in SARS-CoV-2-naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine-booster dose ( identifier: NCT04754698).