Evaluation of the treatment of cutaneous lupus erythematosus with thalidomide: clinical, laboratory and histological factors associated with clinical response and adverse effects

• Grant number: 19/21173-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2019
• Effective date (End): February 28, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Clovis Artur Almeida da Silva
• Grantee: Carolina Torres Ribeiro
• 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

Saliva is suggested as an alternative matrix to individualize and optimize therapy in chronic diseases because of its non-invasive obtention, low complexity compared to conventional matrix and for offering, generally, a good correlation with the free drug in serum. However, few studies have explored the potential for monitoring drugs in this matrix, in part due to the low sensitivity of available quantitative bioanalytical methods. The recent development of high-performance and precision tandem mass spectrometers has made possible to measure very low drug values in small volumes of unconventional matrices. In the area of rheumatology, there are few studies of monitoring of circulating drug levels, and there are no studies of monitoring of thalidomide circulating levels. Thalidomide is an immunomodulatory agent used to treat SLE and lupus skin activity, even in patients refractory to other treatments. Its high efficacy associated with a very rapid response of the skin, made this drug one of choice in patients without contraindication. Thalidomide acts primarily by inhibitingTNF-± synthesis. In addition, thalidomide appears to inhibit B-induced keratinocyte apoptosis. There are several reported adverse effects associated with thalidomide, including dizziness, abdominal pain, and peripheral polyneuropathy, in addition to its known teratogenicity. small fiber neuropathy has recently been reported to be associated with anti-TNF-± therapy, with clinical and skin biopsy findings suggestive of posterior dorsal root involvement in patients with rheumatoid arthritis. In order to better understand the mechanisms involved in thalidomide therapeutic response and adverse effects, we intend to evaluate whether plasma and saliva levels together with tissue expression of TNF-± at the beginning of treatment would be relevant parameters as predictors of response to therapy. In addition, a longitudinal assessment of inflammatory markers and thalidomide serum and saliva concentration will be performed to establish the role of this approach in monitoring the effectiveness of therapy in SLE. (AU)

Scientific publications

(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)

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)