Hydroxychloroquine Blood Levels in Primary Sjögren Syndrome Patients

Study Overview
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Brief Summary
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Introduction. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammatory infiltration of the salivary and lacrimal glands causing dry eye and mouth. Multiple systemic manifestations can also occur. Hydroxychloroquine (HCQ), an antimalarial immunomodulator, has been used for the treatment of arthralgias, myalgia and constitutional symptoms resulting from pSS. However, there are no studies that evaluated whether blood levels of HCQ could influence in the therapeutic response, as has been reported in systemic lupus erythematosus (SLE). Objectives. Analyze in patients with pSS receiving HCQ as part of their treatment: blood levels of HCQ; adherence using a questionnaire versus blood levels and the possible correlation of blood levels with the disease activity score in a cross-sectional evaluation followed by a longitudinal six-month assessment. Patients and methods. Observational cross-sectional evaluation followed by a six-month longitudinal assessment, including patients with pSS receiving HCQ for at least 3 months at study admission. Patients will be evaluated clinically and the HCQ blood level measured at the beginning of the study (T0), at 3 months (T3), and at 6 months (T6). As there are no previous studies on blood levels of HCQ in patients with pSS, the sample of 75 patients was calculated based on the percentage of these patients currently using HCQ in our service (nearly 50%) and in the number of patients in current follow-up (about 150). We will evaluate 75 adult patients with pSS according to the classification criteria of the American-European Consensus Group 2002 and/or the American College of rheumatology (ACR) and the European League Against Rheumatism (EULAR) 2016, of both sexes and followed up regularly at the Sjögren Syndrome outpatient Clinic of the Rheumatology Service of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). The following will be used in the clinical evaluation: the xerostomia Inventory; the xerophthalmia questionnaire - Ocular Surface Disease Index (OSDI); the EULAR Sjögren Syndrome Reported Index (ESSPRI); the EULAR Sjögren Syndrome Disease Activity Index (ESSDAI); the Sjögren's Syndrome Disease Damage Index (SSDDI); the non-stimulated and stimulated salivary flow. Blood levels of HCQ will be measured by high performance liquid chromatography and tandem mass spectrometry.

Official Title
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Analysis of Hydroxychloroquine Blood Levels in Patients With Primary Sjögren Syndrome and Possible Correlation With the Disease Activity

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Other: Parallel Assignment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pSS according to the classification criterias Who have been receiving HCQ for at least 3 months before study entry Patients who agree to participate in the study, according to the signing of the Free and Informed Consent Term (ICF). Exclusion Criteria: Present other associated systemic autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, demato/polymyositis, mixed connective tissue disease, spondyloarthritis, primary biliary cholangitis and autoimmune hepatitis; Present a previous history of radiotherapy of the head and neck, positive serologies for HIV, hepatitis B and C, sarcoidosis, graft versus host disease and IgG4-related disease; Use of drugs that can interact with HCQ or interfere in HCQ blood levels (tamoxifen, antacids and digoxin), alcoholism, current infections, liver and heart failure, dialysis, severe chronic renal failure (serum creatinine ≥3 mg/dL) and pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| pSS patients under Hydroxychloroquine (HCQ) 2016-AAO dose<br>Patients under Hydroxychloroquine (HCQ) 2016-American Academy of ophtalmology (AAO) dose will have HCQ blood levels, disease activity and adherence evaltuated at study entry and before 3 and 6-months. | Other: Parallel Assignment<br>* We will evaluate 75 patients with pSS (Consenso Americano-europeu de 2002 / EULAR/ACR Classification Criteria, 2016) of both sexes at baseline and 6-months<br>* Other names: pSS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of HCQ blood levels at 3 and 6 months | Hydroxychloroquine blood levels will be measure using liquid chromatography tandem Mass Spectrometry (LC-MS/MS), as previously described (PEDROSA et al., 2020). | Baseline, 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCQ adherence in pSS patients | Will be analysed the possible correlation between MTA (measure for treatment adhernce - a quesionnaire of adherence) score and HCQ blood levels em ng/mL (using liquid chromatography tandem Mass Spectrometry (LC-MS/MS), as previously described (PEDROSA et al., 2020). For SLE patients, adherence by HCQ blood levels is defined when HCQ blood levels are >500 ng/mL, this value in pSS patients will be estimated using this 2 assessements | Baseline, 3 and 6 months | 
| Disease activity in pSS patients | We will evaluate the disease activity in pSS patients and correlate if HCQ blood levels can predict risk of disease acrivity | Baseline, 3 and 6 months |