Hydroxychloroquine Blood Levels in Primary Sjögren Syndrome Patients (1ASSJHCQ)

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

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.

Study Overview

• Status: Completed
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Other: Parallel Assignment

• Study Type: Observational
• Enrollment (Actual): 74

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-000
    • Hospital das Clínicas da Faculdade de Medicina da USP
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

pSS patients according to the classification criterias regularly followed at outpatient clinic, Rheumathology division of Hospital das Clinicas da Universidade de Sao Paulo

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
pSS patients under Hydroxychloroquine (HCQ) 2016-AAO dose; 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; 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; Other Names: pSS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• Pedrosa TN, Pasoto SG, Aikawa NE, Yuki EF, Borba EF, Filho JCF, Carricondo PC, Zanetti CB, Conde PG, Duarte NJ, Fontoura N, Romano P, Carvalho VM, Silva CA, Bonfa E. Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis. Lupus. 2020 May;29(6):560-568. doi: 10.1177/0961203320912832. Epub 2020 Mar 19. No abstract available.
• Cankaya H, Alpoz E, Karabulut G, Guneri P, Boyacioglu H, Kabasakal Y. Effects of hydroxychloroquine on salivary flow rates and oral complaints of Sjogren patients: a prospective sample study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Jul;110(1):62-7. doi: 10.1016/j.tripleo.2010.02.032.
• Yavuz S, Asfuroglu E, Bicakcigil M, Toker E. Hydroxychloroquine improves dry eye symptoms of patients with primary Sjogren's syndrome. Rheumatol Int. 2011 Aug;31(8):1045-9. doi: 10.1007/s00296-010-1415-4. Epub 2010 Mar 23.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: 1ASSJ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No