Cutaneous Lupus, Juvenile SLE, Systemic Lupus Erythematosus (SLE)
Conditions
Brief summary
No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. 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. 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 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.
Detailed description
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.
Interventions
DRUGThalidomide
Thalidomide 100 mg/day
DRUGHydroxychloroquine reduced
Hydroxychloroquine 2.5 mg/kg/day
DRUGstandard dose of HCQ
Hydroxychloroquine 5.0 mg/kg/day
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
University of Sao Paulo General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study includes 3 subprojects that will assess serum drug levels for efficacy and toxicity. In the first two subprojects, hydroxychloroquine will be studied in SLE population. In the third subproject, thalidomide and SLE and cutaneous lupus will be studied.
Eligibility
Sex/Gender
ALL
Age
5 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Thalidomide subproject: Inclusion Criteria: * SLE diagnosis according to 1997 ACR criteria * Active and refractory cutaneous lupus lesions * Male gender (using contraceptive barrier method) or confirmed infertility for female gender * Normal electroneuromyography at study entry
Exclusion criteria
* Alcoholism * History of peripheral neuropathy * Previous history of thrombophilia or positive antiphospholipid antibodies * Renal and/or central nervous system and/or hematological activity HCQ reduced subproject: Inclusion Criteria: * SLE diagnosis according to 1997 ACR criteria * Use of hydroxychloroquine (5 to 6.5mg/kg/day) for ≥5 years * SLEDAI-2K \<4
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Thalidomide | 12 months | Serum levels of thalidomide by liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) |
| Serum Levels of Hydroxycloroquine | 12 months | Serum levels of hydroxycloroquine by LCMS |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inactive SLE With Standard Dose of HCQ Lupus nephritis patients on stable inactive disease for at least 6 months prescribed full 2016-AAO dose of HCQ (4-5.5 mg/kg/day, real body weight). | 41 |
| Inactive SLE With Reduced Dose of HCQ Lupus nephritis patients on stable inactive disease for at least 6 months prescribed reduced 2016-AAO dose of HCQ (2-3.0 mg/kg/day, real body weight). | 32 |
| SLE/Cutaneous Lupus With Thalidomide This subproject includes only one arm of lupus patients with active and refractory cutaneous disease and eligible for Thalidomide 100mg/day for 12 months. | 20 |
| Total | 93 |
Baseline characteristics
| Characteristic | Inactive SLE With Standard Dose of HCQ | Inactive SLE With Reduced Dose of HCQ | SLE/Cutaneous Lupus With Thalidomide | Total |
|---|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 10.5 | 37 years STANDARD_DEVIATION 6.9 | 44.8 years STANDARD_DEVIATION 7.6 | 37 years STANDARD_DEVIATION 8.7 |
| Drug blood levels | 1343.5 ng/mL STANDARD_DEVIATION 521.5 | 1404.9 ng/mL STANDARD_DEVIATION 492 | — | 1374.2 ng/mL STANDARD_DEVIATION 506.8 |
| Race/Ethnicity, Customized Caucasian | 13 Participants | 6 Participants | 9 Participants | 28 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 28 Participants | 26 Participants | 11 Participants | 65 Participants |
| Sex: Female, Male Female | 39 Participants | 29 Participants | 17 Participants | 85 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 41 | 0 / 32 |
| other Total, other adverse events | 12 / 20 | 0 / 41 | 0 / 32 |
| serious Total, serious adverse events | 0 / 20 | 0 / 41 | 0 / 32 |
Outcome results
Primary
Serum Levels of Hydroxycloroquine
Serum levels of hydroxycloroquine by LCMS
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SLE/Cutaneous Lupus With Thalidomide | Serum Levels of Hydroxycloroquine | 991.6 ng/mL | Standard Deviation 576.3 |
| Inactive SLE With Reduced Dose of HCQ | Serum Levels of Hydroxycloroquine | 569.0 ng/mL | Standard Deviation 533.4 |
Primary
Serum Levels of Thalidomide
Serum levels of thalidomide by liquid chromatography and tandem mass spectrometry (HPLC-MS/MS)
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SLE/Cutaneous Lupus With Thalidomide | Serum Levels of Thalidomide | 415.1 ng/mL | Standard Deviation 326 |