ANA PAULA LUPPINO ASSAD

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P ICHC, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: CLOVIS ARTUR ALMEIDA DA SILVA ×

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  • article 0 Citação(ões) na Scopus
    Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients
    (2023) SAKAMOTO, Ana P.; SILVA, Clovis A.; PITA, Ana C.; TRINDADE, Vitor C.; ISLABAO, Aline G.; FIOROT, Fernanda J.; LOPES, Sandra R. M.; PEREIRA, Rosa M. R.; SAAD-MAGALHAES, Claudia; RUSSO, Gleice C. S.; LEN, Claudio A.; PRADO, Rogerio do; CAMPOS, Lucia M. A.; AIKAWA, Nadia E.; APPENZELLER, Simone; FERRIANI, Virginia P. L.; SILVA, Marco F.; FELIX, Marta; FONSECA, Adriana R.; ASSAD, Ana P. L.; SZTAJNBOK, Flavio R.; SANTOS, Maria C.; BICA, Blanca E.; SENA, Evaldo G.; MORAES, Ana J.; FRAGA, Melissa M.; ROBAZZI, Teresa C.; SPELLING, Paulo F.; SCHEIBEL, Iloite M.; CAVALCANTI, Andre S.; MATOS, Erica N.; GUIMARAES, Luciano J.; SANTOS, Flavia P.; MOTA, Licia M. H.; BONFA, Eloisa; TERRERI, Maria T.
    Objectives: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients.Methods: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots.Results: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively.Conclusions: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.
  • article 13 Citação(ões) na Scopus
    Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine
    (2022) AIKAWA, Nadia E.; KUPA, Leonard V. K.; SILVA, Clovis A.; SAAD, Carla G. S.; PASOTO, Sandra G.; YUKI, Emily F. N.; FUSCO, Solange R. G.; SHINJO, Samuel K.; ANDRADE, Danieli C. O.; SAMPAIO-BARROS, Percival D.; PEREIRA, Rosa M. R.; CHASIN, Anna C. S.; SHIMABUCO, Andrea Y.; LUPPINO-ASSAD, Ana P.; LEON, Elaine P.; LOPES, Marta H.; ANTONANGELO, Leila; MEDEIROS-RIBEIRO, Ana C.; BONFA, Eloisa
    Objectives. To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods. A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies-NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. Results. Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0 .001) . Negative NAb was associated with older age (P = 0.015), RA (P = 0 .002) , SSc (P = 0 .026) , LEF (P = 0 .01 6) and rituximab use (P = 0.007) . In multiple logistic regression analysis, prednisone dose >= 7.5 mg/day (OR =0.34; P = 0.047) , LEF (OR =0.32, P = 0.036) and rituximab use (OR =0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose. Conclusions. This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose.
  • article 4 Citação(ões) na Scopus
    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, Eloisa
    Characterising 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).
  • article 29 Citação(ões) na Scopus
    Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases
    (2022) AIKAWA, Nadia Emi; KUPA, Leonard de Vinci Kanda; MEDEIROS-RIBEIRO, Ana Cristina; SAAD, Carla Goncalves Schahin; YUKI, Emily Figueiredo Neves; PASOTO, Sandra Gofinet; ROJO, Priscila Tagliaferro; PEREIRA, Rosa Maria Rodrigues; SHINJO, Samuel Katsuyuki; SAMPAIO-BARROS, Percival Degrava; ANDRADE, Danieli Castro Oliveira; HALPERN, Ari Stiel Radu; FULLER, Ricardo; SOUZA, Fernando Henrique Carlos; GUEDES, Lissiane Karine Noronha; ASSAD, Ana Paula Luppino; MORAES, Julio Cesar Bertacini de; LOPES, Michelle Remiao Ugolini; MARTINS, Victor Adriano de Oliveira; BETANCOURT, Lorena; RIBEIRO, Carolina Torres; SALES, Lucas Peixoto; BERTOGLIO, Isabela Maria; BONOLDI, Virginia Lucia Nazario; MELLO, Renata Lys Pinheiro; BALBI, Gustavo Guimaraes Moreira; SARTORI, Ana Marli Christovam; ANTONANGELO, Leila; SILVA, Clovis Artur; BONFA, Eloisa
    Objective To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. Methods Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. Results ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone >= 5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone >= 5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). Conclusions We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.
  • article 9 Citação(ões) na Scopus
    SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy
    (2022) SAMPAIO-BARROS, Percival Degrava; MEDEIROS-RIBEIRO, Ana Cristina; LUPPINO-ASSAD, Ana Paula; MIOSSI, Renata; SILVA, Henrique Carrico da; YUKI, Emily F. V. N.; PASOTO, Sandra G.; SAAD, Carla G. S.; SILVA, Clovis A.; KUPA, Leonard V. K.; DEVEZA, Giordano B. H.; PEDROSA, Tatiana N.; AIKAWA, Nadia E.; BONFA, Eloisa
    Objective. To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) vaccination in patients with SSc. Methods. This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the second dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants. Results. Patients and controls had comparable median ages [48(38.5-57) vs 48(38-57) years, P =0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly MMF (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, P < 0.001) and NAb positivity (53.8% vs 76.9%; P =0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both seroconvertion rates (SC) (P =0.958) and NAb positivity (P =0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC: 31.3% vs 90%, P < 0.001) and NAb(18.8% vs 85%, P < 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95% CI: 0.009, 0.034), P =0.002] and NAb positivity [OR =0.047(95% CI: 0.007, 0.036), P =0.002]. No moderate/severe side-effects were observed. Conclusion. CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients.
  • article 17 Citação(ões) na Scopus
    Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study
    (2018) SETOUE, Debora N.; PITTA, Ana C.; FIOROT, Fernanda J.; NASTRI, Mariana M.; NOVAK, Glaucia V.; MOLINARI, Beatriz C.; OLIVEIRA, Juliana C.; GORMEZANO, Natali W.; SAKAMOTO, Ana P.; TERRERI, Maria T.; PEREIRA, Rosa M.; SAAD-MAGALHAES, Claudia; SALLUM, Adriana M.; KOZU, Katia; FRAGA, Melissa M.; PIOTTO, Daniela P.; CLEMENTE, Gleice; MARINI, Roberto; GOMES, Hugo R.; RABELO-JUNIOR, Carlos N.; FELIX, Marta M.; RIBEIRO, Maria C.; ALMEIDA, Rozana G.; ASSAD, Ana P.; SACCHETTI, Silvana B.; BARROS, Leandra C.; BONFA, Eloisa; SILVA, Clovis A.
    Objective: To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus (cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. Methods: A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. Results: At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). Conclusions: Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.
  • article 12 Citação(ões) na Scopus
    The new 2019-EULAR/ACR classification criteria specific domains at diagnosis can predict damage accrual in 670 childhood-onset systemic lupus erythematosus patients
    (2021) PITTA, Ana C.; SILVA, Clovis A.; INSFRAN, Carlos E.; PASOTO, Sandra G.; TRINDADE, Vitor C.; V, Glaucia Novak; SAKAMOTO, Ana P.; TERRERI, Maria T.; PEREIRA, Rosa M. R.; MAGALHAES, Claudia S.; FONSECA, Adriana R.; ISLABAO, Aline G.; ASSAD, Ana P. L.; BUSCATTI, Izabel M.; ELIAS, Adriana M.; PIOTTO, Daniela P.; FERRIANI, Virginia P.; CARVALHO, Luciana M.; RABELO JUNIOR, Carlos N.; MARINI, Roberto; SZTAJNBOK, Flavio R.; SACCHETTI, Silvana B.; BICA, Blanca E.; MORAES, Ana J.; ROBAZZI, Teresa C.; LOTUFO, Simone; CAVALCANTI, Andre S.; NAKA, Erica N.; CARNEIRO-SAMPAIO, Magda; BONFA, Eloisa; AIKAWA, Nadia E.
    Objective To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). Methods This retrospective multicenter study included 670 cSLE patients with <= 5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI >= 1). Results Median disease duration was 2.8 (IQR 1.8-3.8) years and 200 (29.9%) patients had at least one organ damage (SDI >= 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI >= 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773-24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481-16.399, p<0.0001) at latest visit, respectively. cSLE patients with positive anti-dsDNA at diagnosis were also associated with renal damage by the latest visit (OR 2.438, 95% CI 1.114-5.3381, p = 0.021). Constitutional, hematologic, mucocutaneous, serosal, and musculoskeletal domains and specific criteria as well as other immunologic criteria were not associated with damage accrual. Median of SLEDAI-2K was significantly higher in patients with global damage (19.5 (2-51) vs 14 (0-51), p<0.001). 2019-EULAR/ACR score >25 was associated with more overall (SDI >= 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). Conclusions The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25.