Hydroxychloroquine and Sjögren's disease: current evidences for its use

Area of Science:

• Immunology
• Rheumatology
• Pharmacology

Background:

• Hydroxychloroquine (HCQ) is frequently prescribed for primary Sjögren's disease (SjD), despite limited high-quality evidence.
• Its use is largely based on expert opinion and clinical experience rather than robust clinical trial data.

Purpose of the Study:

• To comprehensively review the pathogenic mechanisms, clinical evidence, and safety of HCQ in primary SjD.
• To evaluate the current understanding of HCQ's role in managing Sjögren's disease.

Main Methods:

• Review of existing literature on HCQ's immunomodulatory effects.
• Analysis of clinical trial data, including randomized controlled trials (RCTs) and observational studies.
• Examination of safety profiles and benefit-risk assessments.

Main Results:

• HCQ exhibits immunomodulatory effects by regulating interferon proteins, chemokines, BAFF, and gut microbiota, decreasing immunoglobulin and ESR levels.
• Clinical evidence is primarily from open-label or retrospective studies; only three RCTs exist, with the JOQUER trial failing to show significant improvement in key Sjögren's disease metrics.
• Subgroup analysis of the JOQUER trial suggested potential benefits on the ESSPRI score, and preliminary data on HCQ/leflunomide combination therapy shows promise.

Conclusions:

• HCQ remains a central treatment for primary Sjögren's disease due to its favorable benefit-risk profile, despite inconclusive evidence from RCTs.
• Further research, including ongoing studies like NECESSITY, is needed to clarify HCQ's efficacy, particularly regarding long-term outcomes like damage accrual, quality of life, and mortality.