Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases

University of Sao Paulo General Hospital

Status and phase: Completed; Phase 4

Conditions: Juvenile SLE; Cutaneous Lupus; Systemic Lupus Erythematosus (SLE)

Treatments: Drug: Thalidomide; Drug: standard dose of HCQ; Drug: Hydroxychloroquine reduced

Study type: Interventional

Funder types: Other

Identifiers

NCT03122431

HPLC-Rheumatic diseases

Details and patient eligibility

About

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.

Full 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.

Enrollment: 93 patients

Sex: All

Ages: 5 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Exclusion Criteria:

• Alcoholism
• Renal dialysis
• Concomitant infectious process
• Acute and chronic liver diseases
• Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
• Signs of Retinopathy

HCQ high subproject:

Inclusion Criteria:

• SLE diagnosis according to 1997 ACR criteria
• No use of hydroxychloroquine for ≥ 6 months
• LES/LESJ in activity (SLEDAI≥6)

Exclusion Criteria:

• Alcoholism
• Renal dialysis
• Concomitant infectious process
• Acute and chronic liver diseases
• Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
• Signs of Retinopathy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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93 participants in 3 patient groups

SLE/cutaneous lupus with thalidomide

Other group

Description:

This subproject includes only one arm of lupus patients with active and refractory cutaneous disease and eligible for Thalidomide 100mg/day for 12 months.

Treatment:

Drug: Thalidomide

Inactive SLE with standard dose of HCQ

Active Comparator group

Description:

This subproject includes one arm of lupus patients with inactive disease, in which will be maintained on standard dose of Hydroxychloroquine (400mg/day).

Treatment:

Drug: standard dose of HCQ

Inactive SLE with reduced dose of HCQ

Active Comparator group

Description:

This subproject includes one arm of lupus patients with inactive disease: in which the dose will be reduced to 400mg 3 times a week (Hydroxychloroquine reduced).

Treatment:

Drug: Hydroxychloroquine reduced