Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy

• Grant number: 17/14352-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2017
• End date: May 19, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Clovis Artur Almeida da Silva
• Grantee: Tatiana Do Nascimento Pedrosa
• 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

(17)

(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)

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)

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)

PEDROSA, TATIANA N.; PASOTO, SANDRA G.; AIKAWA, NADIA E.; YUKI, EMILY F. N.; BORBA, EDUARDO F.; FERREIRA FILHO, JULIO C. R.; CARRICONDO, PEDRO C.; ZANETTI, CAIO B.; CONDE, PAOLA G.; DUARTE, NILO J. C.; et al. Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis. Lupus, v. 29, n. 6, MAR 2020. (15/03756-4, 17/11516-9, 17/11854-1, 17/14352-7, 17/11644-7)

BALBI, VERENA ANDRADE; SILVA, CLOVIS ARTUR; PEDROSA, TATIANA NASCIMENTO; RODRIGUES PEREIRA, ROSA MARIA; DE ARRUDA CAMPOS, LUCIA MARIA; LEON, ELAINE PIRES; DUARTE, NILO; CARVALHO, VALDEMIR MELECHCO; PASOTO, SANDRA GOFINT; DO ROSARIO, DEBORA CORDEIRO; et al. ydroxychloroquine blood levels predicts flare in childhood-onset lupus nephriti. Lupus, v. 31, n. 1, DEC 2021. (17/14352-7, 15/03756-4)

CLAUDINO FORMIGA, FRANCISCO FELLIPE; SILVA, CLOVIS ARTUR; PEDROSA, TATIANA DO NASCIMENTO; AIKAWA, NADIA EMI; PASOTO, SANDRA GOFINET; GARCIA, CRISTIANA COUTO; VIDAL CAPAO, ARTUR SILVA; DE OLIVEIRA MARTINS, VICTOR ADRIANO; TONACIO DE PROENCA, ADRIANA CORACINI; FULLER, RICARDO; et al. Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity. Lupus, v. 30, n. 12, AUG 2021. (18/09937-9, 17/14352-7, 10/10749-0, 15/03756-4, 18/16162-3)

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)

MUNHOZ, GABRIELA A.; AIKAWA, NADIA E.; SILVA, CLOVIS A.; PASOTO, SANDRA G.; PEDROSA, TATIANA N.; SEGURO, LUCIANA P. C.; BONFA, ELOISA; BORBA, EDUARDO F.. Short-term Accrual 2019 European League Against Rheumatism/American College of Rheumatology Domains and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage in Lupus Patients With and Without Nephritis at Disease Onset. JCR-JOURNAL OF CLINICAL RHEUMATOLOGY, v. 29, n. 4, p. 6-pg., 2023-06-01. (17/14352-7, 18/16162-3, 15/03756-4)

NADIA EMI AIKAWA; EDUARDO FERREIRA BORBA; VERENA ANDRADE BALBI; ADRIANA MALUF ELIAS SALLUM; IZABEL MANTOVANI BUSCATTI; LUCIA MARIA ARRUDA CAMPOS; KÁTIA TOMIE KOZU; CRISTIANA COUTO GARCIA; ARTUR SILVA VIDAL CAPÃO; ADRIANA CORACINI TONACIO DE PROENÇA; et al. Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus. ADVANCES IN RHEUMATOLOGY, v. 63, 2023-12-18. (17/14352-7, 18/16162-3, 15/03756-4, 10/10749-0)

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)

TONACIO, ADRIANA CORACINI; PEDROSA, TATIANA DO NASCIMENTO; BORBA, EDUARDO FERREIRA; AIKAWA, NADIA EMI; PASOTO, SANDRA GOFINET; RENTE FERREIRA FILHO, JULIO CESAR; SAMPAIO BARROS, MARILIA MANTOVANI; LEON, ELAINE PIRES; FERREIRA SPINA LOMBARDI, SUZETE CLEUSA; MENDRONE JUNIOR, ALFREDO; et al. mmunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic disease. PLoS Neglected Tropical Diseases, v. 15, n. 11, NOV 2021. (10/10749-0, 17/14352-7, 18/16162-3, 17/11516-9)

MEDEIROS-RIBEIRO, ANA C.; AIKAWA, NADIA E.; SAAD, CARLA G. S.; YUKI, EMILY F. N.; PEDROSA, TATIANA; FUSCO, SOLANGE R. G.; ROJO, PRISCILA T.; PEREIRA, ROSA M. R.; SHINJO, SAMUEL K.; ANDRADE, DANIELI C. O.; et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nature Medicine, v. 27, n. 10, JUL 2021. (18/09937-9, 17/14352-7, 19/21173-7, 15/03756-4, 20/11677-5)

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)

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)

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.. Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease. Lupus, v. 31, n. 6, p. 7-pg., 2022-03-25. (15/03756-4, 17/14352-7, 14/03742-0)

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)

PASOTO, SANDRA GOFINET; BORBA, EDUARDO FERREIRA; FORMIGA, FRANCISCO FELLIPE CLAUDINO; DO NASCIMENTO PEDROSA, TATIANA; AIKAWA, NADIA EMI; DE SIQUEIRA, MARILDA AGUDO MENDONCA TEIXEIRA; CAPAO, ARTUR SILVA VIDAL; DE PROENCA, ADRIANA CORACINI TONACIO; FULLER, RICARDO; YUKI, EMILY FIGUEIREDO NEVES; et al. Robust immunogenicity to the H3N2 component of influenza A vaccine in primary Sjogren syndrome. CLINICAL RHEUMATOLOGY, v. 42, n. 9, p. 7-pg., 2023-06-12. (17/14352-7, 18/16162-3, 15/03756-4)