Is Plaquenil (hydroxychloroquine) and Leflunomide a solid treatment for overlapping syndrome with Sjögren's syndrome?

From the Guidelines

Hydroxychloroquine (Plaquenil) and leflunomide can be considered a solid treatment for overlapping syndrome with Sjögren's syndrome, based on the latest recommendations from the European League Against Rheumatism (EULAR) 1. The EULAR recommendations suggest hydroxychloroquine (HCQ) 200 mg/day as a treatment option for patients with primary Sjögren's syndrome (SjS) presenting with organ-specific systemic involvements 1.

• Key points to consider when using this combination include:
  • Hydroxychloroquine is often used as a first-line treatment for Sjögren's syndrome to manage symptoms such as fatigue, joint pain, and skin manifestations.
  • Leflunomide can be added to the treatment regimen when there are significant inflammatory arthritis symptoms that don't respond adequately to hydroxychloroquine alone.
  • The combination of hydroxychloroquine and leflunomide targets different inflammatory pathways, providing a comprehensive approach to managing the condition.
  • Regular monitoring is essential to minimize the risk of adverse effects, including eye exams every 6-12 months for hydroxychloroquine and liver function tests for leflunomide 1. The EULAR recommendations also highlight the importance of considering other treatment options, such as glucocorticoids, immunosuppressive agents, and biologic agents, depending on the specific organ involvement and symptom severity 1.
• In terms of specific treatment approaches, the EULAR algorithm suggests the following:
  • NSAIDs for short-term use (no longer than 7-10 days)
  • Hydroxychloroquine 200 mg/day
  • Glucocorticoids (short-term course whenever possible)
  • Immunomodulators, such as cyclophosphamide, rituximab, and belimumab, for patients with severe or refractory disease 1.

From the Research

Treatment of Overlapping Syndrome with Sjögren's Syndrome

• The use of Plaquenil (hydroxychloroquine) and Leflunomide as a treatment for overlapping syndrome with Sjögren's syndrome has been studied in several research papers 2, 3, 4, 5, 6.
• A study published in 2014 found that hydroxychloroquine did not improve symptoms in patients with primary Sjögren's syndrome during 24 weeks of treatment 2.
• However, a study published in 2020 found that the combination of leflunomide and hydroxychloroquine resulted in a clinical response in patients with primary Sjögren's syndrome, with a mean difference in ESSDAI score of -4.35 points compared to the placebo group 3.
• Another study published in 2019 found that the combination of leflunomide and hydroxychloroquine additively inhibited immune activation in patients with primary Sjögren's syndrome, supporting the potential implementation of this drug combination in treatment 4.
• A retrospective study published in 2022 found that hydroxychloroquine therapy was not associated with significantly lower immunoglobulin levels in women with IgG subclass deficiency and systemic lupus erythematosus, Sjögren syndrome, or rheumatoid arthritis 5.
• A review article published in 2017 discussed the diagnosis and treatment of Sjögren's syndrome, highlighting the complexity of the disease and the need for interdisciplinary treatment 6.

Efficacy of Plaquenil and Leflunomide

• The efficacy of Plaquenil and Leflunomide in treating overlapping syndrome with Sjögren's syndrome is supported by some studies, which found that the combination of these two drugs resulted in a clinical response in patients with primary Sjögren's syndrome 3, 4.
• However, other studies found that hydroxychloroquine did not improve symptoms in patients with primary Sjögren's syndrome during 24 weeks of treatment 2.
• The use of Plaquenil and Leflunomide as a treatment for overlapping syndrome with Sjögren's syndrome may be considered on a case-by-case basis, taking into account the individual patient's symptoms and disease activity.

Safety and Side Effects

• The safety and side effects of Plaquenil and Leflunomide have been studied in several research papers 2, 3, 4, 5.
• Common side effects of leflunomide and hydroxychloroquine include gastrointestinal discomfort, modest transient increases in alanine aminotransferase, and short episodes of general malaise and shivering 3.
• Hydroxychloroquine therapy was not associated with significantly lower immunoglobulin levels in women with IgG subclass deficiency and systemic lupus erythematosus, Sjögren syndrome, or rheumatoid arthritis 5.