Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
Condition: Systemic Lupus Erythematosus (SLE); Juvenile SLE; Cutaneous Lupus
MeSH terms: Lupus Erythematosus, Systemic; Autoimmune Diseases
Intervention: Thalidomide; Hydroxychloroquine reduced; standard dose of HCQ
Intervention description: Thalidomide 100 mg/day; Hydroxychloroquine 2.5 mg/kg/day; Hydroxychloroquine 5.0 mg/kg/day
Intervention MeSH terms: Hydroxychloroquine; Thalidomide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: None (Open Label)
Enrollment: 93.0
Sex: All
Minimum age: 5 Years
Maximum age: 64 Years
Healthy volunteers: No

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.
    

Eligibility 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