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  • article 0 Citação(ões) na Scopus
    Thalidomide measurement in plasma and dried plasma spot by SPE combined with UHPLC-MS/MS for therapeutic drug monitoring
    (2022) NOVELLINO, Renata Soares; CHALOM, Marc Yves; ROMANO, Paschoalina; EBNER, Persio de Almeida Rezende; SERAPHIM, Julia Celestino; AMARAL, Ana Carolina Silva do; DUARTE, Nilo Jose Coelho; PEDROSA, Tatiana Do Nascimento; YUKI, Emily Figueiredo Neves; AIKAWA, Nadia Emi; PASOTO, Sandra Gofinet; SILVA, Clovis Artur Almeida da; CARVALHO, Valdemir Melechco; BONFA, Eloisa; KUPA, Leonard de Vinci Kanda
    Tweetable abstract Thalidomide measurement in dried plasma spot by ultra-HPLC-MS/MS combined with online SPE was successfully validated and applied in therapeutic drug monitoring. #thalidomide #DPS #chromatography #mass spectrometry Aims: To validate an SPE-ultra-HPLC-MS/MS method for thalidomide (THD) measurement in dried plasma spot (DPS). Methods: Extraction included acetonitrile/water clean-up and online SPE. The LOD, LLOQ, linearity, precision, accuracy, recovery, matrix effect, process efficiency, carryover, stability, drug interference and dilution integrity were assessed. Results: The method was linear from 50 to 2000 ng/ml with a LOD of 20 ng/ml and LLOQ of 50 ng/ml. The coefficient of variation for precision was 0.4-7.9% for intra-assay and 1.3-8.9% for interassay and accuracy was 81.4-97.1%. Adequate matrix effect (100.6-107.0%), recovery (88.7-105.0%) and process efficiency (91.3-109.3%) were registered. DPS was stable for 14 days at room temperature and 45 degrees C and for 4 months at -80 degrees C. The method was applied to quantify THD in both wet plasma and DPS from patients with cutaneous lupus receiving THD treatment. The difference between THD wet plasma and DPS concentration was Conclusion: The method is suitable to quantify THD in DPS.
  • conferenceObject
    SARS-COV-2 VACCINE IN SPONDYLOARTHRITIS PATIENTS: OVERALL MODERATE/HIGH IMMUNOGENICITY IMPAIRED BY IMMUNOSUPPRESSANTS AND BIOLOGICAL THERAPY
    (2022) SAAD, C.; SILVA, M. Rodrigues; SAMPAIO-BARROS, P. Degrava; MORAES, J.; GOLDENSTEIN-SCHAINBERG, C.; AIKAWA, N.; NEVES, E.; PASOTO, S.; PEDROSA, T.; AOYAMA, R. Kenji; ARAUJO, C. Scognamiglio Renner; SILVA, C.; RIBEIRO, A. C. Medeiros; BONFA, E.
  • article 22 Citação(ões) na Scopus
    Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study
    (2022) AIKAWA, Nadia E.; KUPA, Leonard V. K.; PASOTO, Sandra G.; MEDEIROS-RIBEIRO, Ana C.; YUKI, Emily F. N.; SAAD, Carla G. S.; PEDROSA, Tatiana; FULLER, Ricardo; SHINJO, Samuel K.; SAMPAIO-BARROS, Percival D.; ANDRADE, Danieli C. O.; PEREIRA, Rosa M. R.; SEGURO, Luciana P. C.; VALIM, Juliana M. L.; WARIDEL, Filipe; SARTORI, Ana Marli C.; DUARTE, Alberto J. S.; ANTONANGELO, Leila; SABINO, Ester C.; MENEZES, Paulo Rossi; KALLAS, Esper G.; SILVA, Clovis A.; BONFA, Eloisa
    Background We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. Methods CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo) in Sao Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 mu g in 0middot5 mL of beta-propiolactone inactivated SARSCoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15middot0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of >= 30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARSCoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. Findings Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52middot3 [95% CI 42middot9-63middot9] at day 0 vs 128middot9 [105middot6-157middot4] at day 28; seropositive controls 53middot3 [45middot4-62middot5] at day 0 vs 202middot0 [174middot8-233middot4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137middot1 [116middot2-161middot9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188middot6 [167middot4-212middot6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2middot3 (95% CI 2middot2-2middot3) at day 0, 5middot7 (5middot1-6middot4) at day 28, and 29middot6 (26middot4-33middot3) at day 69, and in seronegative controls were 2middot3 (2middot1-2middot5) at day 0, 10middot6 (8middot7-13middot1) at day 28, and 71middot7 (63middot5-81middot0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. Interpretation By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients.
  • article 12 Citação(ões) na Scopus
    Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2
    (2022) SHINJO, Samuel K.; SOUZA, Fernando H. C. de; BORGES, Isabela B. P.; SANTOS, Alexandre M. Dos; MIOSSI, Renata; MISSE, Rafael G.; MEDEIROS-RIBEIRO, Ana C.; SAAD, Carla G. S.; YUKI, Emily F. N.; PASOTO, Sandra G.; KUPA, Leonard V. K.; CENEVIVA, Carina; SERAPHIM, Julia C.; PEDROSA, Tatiana N.; VENDRAMINI, Margarete B. G.; SILVA, Clovis A.; AIKAWA, Nadia E.; BONFA, Eloisa
    Objectives. To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. Methods. This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Results. Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naive participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT [7.9 (95%CI 4.7-13.2) vs 24.7 (95%CI 30.0-30.5) UA/ml, P<0.001] and frequency of NAb (51.4% vs 77.2%, P<0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4-83.4) vs 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P>0.05). Conclusion. Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity.
  • article 12 Citação(ões) na Scopus
    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, Eloisa
    Objective 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 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 8 Citação(ões) na Scopus
    Inactivated SARS-CoV-2 vaccine in primary Sjogren's syndrome: humoral response, safety, and effects on disease activity
    (2022) PASOTO, Sandra Gofinet; HALPERN, Ari Stiel Radu; GUEDES, Lissiane Karine Noronha; RIBEIRO, Ana Cristina Medeiros; YUKI, Emily Neves Figueiredo; SAAD, Carla Goncalves Schahin; SILVA, Clovis Artur Almeida da; KUPA, Leonard de Vinci Kanda; VILLAMARIN, Lorena Elizabeth Betancourt; MARTINS, Victor Adriano de Oliveira; MARTINS, Carolina Campagnoli Machado Freire; DEVEZA, Giordano Bruno Henriques; LEON, Elaine Pires; BUENO, Cleonice; PEDROSA, Tatiana Nascimento; SANTOS, Roseli Eliana Beseggio; SOARES, Renata; AIKAWA, Nadia Emi; BONFA, Eloisa
    Introduction There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjogren's syndrome (pSS). Objectives To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS. Methods Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjogren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile. Results Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p= 1.000) and mean age (53.5 +11.7 vs. 53.4 +11.4 years, p= 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p< 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p< 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p= 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p= 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p> 0.05). Conclusion Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients.
  • article 40 Citação(ões) na Scopus
    Safety and immunogenicity of CoronaVac in people living with HIV: a prospective cohort study
    (2022) NETTO, Lucas C.; IBRAHIM, Karim Y.; PICONE, Camila M.; ALVES, Ana Paula P. S.; V, Eliane Aniceto; SANTIAGO, Mariana R.; PARMEJANI, Patricia S. S.; AIKAWA, Nadia E.; MEDEIROS-RIBEIRO, Ana C.; PASOTO, Sandra G.; YUKI, Emily F. N.; SAAD, Carla G. S.; PEDROSA, Tatiana; LARA, Amanda N.; CENEVIVA, Carina; BONFA, Eloisa; KALLAS, Esper G.; I, Vivian Avelino-Silva
    Background People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression. Methods In this prospective cohort study, adults (aged >= 18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose (day 69). Immunogenicity was assessed at baseline (day 0), before second vaccine (day 28), and 6 weeks after second vaccine dose (day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody (NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres (FI-GMT). We investigated whether HIV status and CD4 count (<500 or 500 cells per mu L) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex. Findings Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 (42%) were people with HIV and 296 (58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose (day 69), 185 (91%) of 204 participants with HIV and 265 (97%) of 274 participants with no known immunosuppression had seroconversion (p=0.0055). 143 (71%) of 202 participants with HIV were NAb positive compared with 229 (84%) of 274 participants with no known immunosuppression (p=0.0008). Median IgG titres were 48.7 AU/mL (IQR 26.6.88.2) in people with HIV compared with 75.2 AU/mL (50.3.112.0) in people with no known immunosuppression (p<0.0001); and median NAb activity was 46.2% (26.9.69.7) compared with 60.8% (39.8.79.9; p<0.0001). In people with HIV who had CD4 counts less than 500 cells per .L seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per .L. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per .L and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per .L. No serious adverse reactions were reported during the study. Interpretation Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV. Funding Fundacao de Amparo a Pesquisa do Estado de S.o Paulo (FAPESP), Conselho Nacional de Desenvolvimento Cientifico e Tecnol.gico (CNPq), and B3.Bolsa de Valores do Brasil.
  • article 40 Citação(ões) na Scopus
    Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial
    (2022) ARAUJO, Carlo Scognamiglio Renner; MEDEIROS-RIBEIRO, Ana Cristina; SAAD, Carla G. S.; BONFIGLIOLI, Karina Rossi; DOMICIANO, Diogo Souza; SHIMABUCO, Andrea Yukie; SILVA, Matheus Santos Rodrigues; YUKI, Emily Figueiredo Neves; PASOTO, Sandra Gofinet; PEDROSA, Tatiana; KUPA, Leonard de Vinci Kanda; ZOU, Gioanna; PEREIRA, Rosa M. R.; SILVA, Clovis Artur; AIKAWA, Nadia Emi; BONFA, Eloisa
    Objective To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). Methods This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) <= 10, prednisone <= 7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice. Results Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024). Conclusion We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.
  • conferenceObject
    A RANDOMIZED CLINICAL TRIAL OF 2-WEEK METHOTREXATE DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS VACCINATED WITH INACTIVATED SARS-COV-2 VACCINE
    (2022) ARAUJO, C. Scognamiglio Renner; RIBEIRO, A. C. Medeiros; SAAD, C.; BONFIGLIOLI, K.; DOMICIANO, D. S.; SHIMABUCO, A. Yukie; SILVA, M. Rodrigues; NEVES, E.; PASOTO, S.; PEDROSA, T.; KUPA, L. Kanda; ZOU, G.; PEREIRA, R. M.; SILVA, A.; AIKAWA, N.; BONFA, E.