Relevance of monitoring blood levels compared to salivar levels of drugs used in rheumatic autoimmune diseases: adherence and understanding the possible underlying mechanisms involved in effectiveness and in adverse effects

• Grant number: 19/17272-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2019
• End date: February 28, 2023
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Eloisa Silva Dutra de Oliveira Bonfá
• Grantee: Leonard de Vinci Kanda Kupa
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy, AP.TEM

Abstract

No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. There is also a large inter-individual variability in response to treatments with regard to efficacy and toxicity, and for many drugs, there is also a period of weeks to months to establish its efficacy. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. The implementation of this methodology dedicated to research in our center, with the necessary training of human resources, will enable the standardization and availability of this advanced technology to other muldisciplinary projects in various areas of science. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This thematic project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids

Scientific publications

(18)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANETTI, CAIO B.; PEDROSA, TATIANA; KUPA, LEONARD DE V. K.; AIKAWA, NADIA E.; BORBA, EDUARDO F.; VENDRAMINI, MARGARETE B. G.; SILVA, CLOVIS A.; PASOTO, SANDRA G.; BONFA, ELOISA. Hydroxychloroquine blood levels in stable lupus nephritis under low dose (2-3 mg/kg/day): 12-month prospective randomized controlled trial. CLINICAL RHEUMATOLOGY, v. 40, n. 7, JAN 2021. (17/14352-7, 19/17272-0, 15/03756-4, 17/03983-6)

SHINJO, SAMUEL K.; DE SOUZA, FERNANDO H. C.; BORGES, ISABELA B. P.; DOS SANTOS, ALEXANDRE M.; MIOSSI, RENATA; MISSE, RAFAEL G.; MEDEIROS-RIBEIRO, ANA C.; SAAD, CARLA G. S.; YUKI, EMILY F. N.; PASOTO, SANDRA G.; et al. Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2. RHEUMATOLOGY, v. N/A, p. 11-pg., 2021-10-19. (19/17272-0, 19/21211-6, 19/11776-6, 15/03756-4)

YUKI, EMILY FIGUEIREDO NEVES; SOARES, RENATA; KUPA, LEONARD DE VINCI KANDA; HEISE, CARLOS OTTO; AIKAWA, NADIA EMI; ARNONE, MARCELO; ROMITI, RICARDO; PEDROSA, TATIANA DO NASCIMENTO; SILVA, CLOVIS ARTUR ALMEIDA DA; BONFA, ELOISA; et al. One-year prospective nerve conduction study of thalidomide neuropathy in lupus erythematosus: Incidence, coasting effect and drug plasma levels. Lupus, v. 30, n. 6, MAR 2021. (15/03756-4, 19/17272-0, 17/14352-7)

PEDROSA, TATIANA; KUPA, LEONARD DE VINCI KANDA; AIKAWA, NADIA EMI; PASOTO, SANDRA GOFINET; BONFA, ELOISA; SILVA, CLOVIS ARTUR. Lupus nephritis-related issues during COVID-19 pandemic quarantine. Lupus, v. 29, n. 14, SEP 2020. (17/14352-7, 19/17272-0, 15/03756-4, 17/03983-6)

ROSA M.R. PEREIRA; MARILIA A. DAGOSTIN; VALERIA F. CAPARBO; LUCAS P. SALES; SANDRA G. PASOTO; CLOVIS A. SILVA; EMILY F.N. YUKI; CARLA G.S. SAAD; ANA C. MEDEIROS-RIBEIRO; LEONARD V.K. KUPA; et al. Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose. Clinics, v. 78, 2023-02-27. (19/17272-0, 15/03756-4, 20/09367-8, 21/08455-3, 18/09937-9)

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.; et al. Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients. NATURE COMMUNICATIONS, v. 13, n. 1, p. 9-pg., 2022-10-03. (15/03756-4, 18/09937-9, 20/09367-8, 19/17272-0)

NOVELLINO, RENATA SOARES; CHALOM, MARC YVES; ROMANO, PASCHOALINA; REZENDE EBNER, PERSIO DE ALMEIDA; SERAPHIM, JULIA CELESTINO; SILVA DO AMARAL, ANA CAROLINA; COELHO DUARTE, NILO JOSE; PEDROSA, TATIANA DO NASCIMENTO; NEVES YUKI, EMILY FIGUEIREDO; AIKAWA, NADIA EMI; et al. Thalidomide measurement in plasma and dried plasma spot by SPE combined with UHPLC-MS/MS for therapeutic drug monitoring. BIOANALYSIS, v. 14, n. 15, p. 12-pg., 2022-09-20. (19/17272-0, 17/03983-6, 19/21211-6, 15/03756-4)

PASOTO, SANDRA GOFINET; HALPERN, ARI STIEL RADU; NORONHA GUEDES, LISSIANE KARINE; MEDEIROS RIBEIRO, ANA CRISTINA; FIGUEIREDO YUKI, EMILY NEVES; SCHAHIN SAAD, CARLA GONCALVES; ALMEIDA DA SILVA, CLOVIS ARTUR; KANDA KUPA, LEONARD DE VINCI; BETANCOURT VILLAMARIN, LORENA ELIZABETH; DE OLIVEIRA MARTINS, VICTOR ADRIANO; et al. Inactivated SARS-CoV-2 vaccine in primary Sjogren's syndrome: humoral response, safety, and effects on disease activity. CLINICAL RHEUMATOLOGY, v. 41, n. 7, p. 11-pg., 2022-03-19. (20/11677-5, 20/09367-8, 19/17272-0, 17/14352-7, 15/03756-4, 18/09937-9, 21/08455-3)

DUARTE, NILO J. C.; KUPA, LEONARD V. K.; FERREIRA-FILHO, JULIO C. R.; FONTOURA, NICOLE; CHALOM, MARC Y.; ROMANO, PASCHOALINA; EBNER, PERSIO A. R.; SILVA, CLOVIS A. A.; CARVALHO, VALDEMIR M.; BONFA, ELOISA. UHPLC-MS/MS Method for Determination of Hydroxychloroquine and Its Main Metabolites in Oral Fluid and Whole Blood for Therapeutic Drug Monitoring. JOURNAL OF APPLIED LABORATORY MEDICINE, v. 6, n. 4, p. 868-880, JUL 2021. (15/03756-4, 17/11644-7, 17/11516-9, 19/17272-0, 17/03983-6)

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.; et al. mmunogenicity 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 stud. LANCET RHEUMATOLOGY, v. 4, n. 2, p. E113-E124, FEB 2022. (17/14352-7, 19/17272-0, 15/03756-4)

PEDROSA, TATIANA; KANDA KUPA, LEONARD DE VINCI; PASOTO, SANDRA GOFINET; AIKAWA, NADIA EMI; BORBA, EDUARDO FERREIRA; DUARTE, NILO J. C.; LEON, ELAINE PIRES; SILVA, CLOVIS ARTUR; BONFA, ELOISA. The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients. Lupus, v. 30, n. 4, p. 554-559, APR 2021. (19/17272-0, 15/03756-4, 17/14352-7, 17/03983-6)

AIKAWA, NADIA EMI; KANDA KUPA, LEONARD DE VINCI; MEDEIROS-RIBEIRO, ANA CRISTINA; SCHAHIN SAAD, CARLA GONCALVES; NEVES YUKI, EMILY FIGUEIREDO; PASOTO, SANDRA GOFINET; ROJO, PRISCILA TAGLIAFERRO; RODRIGUES PEREIRA, ROSA MARIA; SHINJO, SAMUEL KATSUYUKI; SAMPAIO-BARROS, PERCIVAL DEGRAVA; et al. Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases. ANNALS OF THE RHEUMATIC DISEASES, v. 81, n. 7, p. 8-pg., 2022-03-10. (20/09367-8, 19/17272-0, 15/03756-4, 18/09937-9)

MEDEIROS-RIBEIRO, ANA CRISTINA; BONFIGLIOLI, KARINA ROSSI; DOMICIANO, DIOGO SOUZA; SHIMABUCO, ANDREA YUKIE; DA SILVA, HENRIQUE CARRICO; SAAD, CARLA G. S.; YUKI, EMILY FIGUEIREDO NEVES; PASOTO, SANDRA GOFINET; RENNER ARAUJO, CARLO SCOGNAMIGLIO; NAKAI, TATIANE LIE; et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. ANNALS OF THE RHEUMATIC DISEASES, v. 81, n. 5, p. 10-pg., 2022-02-07. (21/06613-0, 17/14352-7, 19/17272-0, 15/03756-4)

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.; et al. Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome. Lupus, v. 31, n. 8, p. 11-pg., 2022-05-20. (19/17272-0, 15/03756-4)

CLOVIS ARTUR SILVA; LEONARD DE VINCI KANDA KUPA; ANA CRISTINA MEDEIROS-RIBEIRO; SANDRA GOFINET PASOTO; CARLA GONÇALVES SCHAHIN SAAD; EMILY FIGUEIREDO NEVES YUKI; JOAQUIM IVO VASQUES DANTAS LANDIM; VICTOR HUGO FERREIRA E LÉDA; LUISA SACCHI DE CAMARGO CORREIA; ARTUR FONSECA SARTORI; et al. Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition. ADVANCES IN RHEUMATOLOGY, v. 63, 2023-09-01. (22/09565-0, 22/09566-6, 19/17272-0, 19/21173-7, 15/03756-4, 21/08455-3, 18/09937-9)

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.; DE ANDRADE, DANIELI C. O.; KUPA, LEONARD DE VINCI K.; et al. Impact of Distinct Therapies on Antibody Response to SARS-CoV-2 Vaccine in Systemic Lupus Erythematosus. ARTHRITIS CARE & RESEARCH, v. 74, n. 4, p. 10-pg., 2022-03-04. (15/03756-4, 17/14352-7, 19/17272-0, 21/06615-3)

SAMPAIO-BARROS, PERCIVAL DEGRAVA; MEDEIROS-RIBEIRO, ANA CRISTINA; LUPPINO-ASSAD, ANA PAULA; MIOSSI, RENATA; DA SILVA, HENRIQUE CARRICO; YUKI, EMILY F. V. N.; PASOTO, SANDRA G.; SAAD, CARLA G. S.; SILVA, CLOVIS A.; KUPA, LEONARD V. K.; et al. SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy. RHEUMATOLOGY, v. 61, n. SI2, p. 6-pg., 2021-12-11. (15/03756-4, 19/17272-0)

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.; et al. Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine. RHEUMATOLOGY, v. N/A, p. 6-pg., 2022-05-26. (15/03756-4, 19/17272-0)