What is the recommended treatment approach for a patient with overlapping syndrome and Sjögren's syndrome being treated with Leflunomide ( Disease-Modifying Antirheumatic Drug (DMARD)) and Plaquenil (Hydroxychloroquine)?

From the Guidelines

For patients with overlapping syndrome and Sjögren's syndrome currently on Leflunomide and Hydroxychloroquine (Plaquenil), the recommended treatment approach is to continue this combination therapy with regular monitoring for efficacy and side effects. The standard maintenance dose for Leflunomide is typically 10-20 mg daily, while Hydroxychloroquine is usually prescribed at 200-400 mg daily (not exceeding 5 mg/kg/day based on ideal body weight) 1. This combination addresses multiple immune pathways involved in these complex autoimmune conditions. Regular laboratory monitoring should include complete blood counts, liver function tests every 1-3 months initially, then quarterly once stable. For Hydroxychloroquine, baseline and annual eye examinations are essential to monitor for retinal toxicity. Patients should be assessed for clinical response every 3-6 months, with treatment adjustments based on disease activity. If symptoms persist despite this combination, adding low-dose corticosteroids (prednisone 5-10 mg daily) temporarily may help manage flares. This multi-targeted approach is effective because Leflunomide inhibits pyrimidine synthesis in rapidly dividing immune cells, while Hydroxychloroquine interferes with antigen processing and cytokine production, collectively addressing the complex immunological disturbances in overlapping autoimmune syndromes.

Some key considerations in managing these patients include:

• Monitoring disease activity and adjusting treatment accordingly 1
• Considering the addition of other medications, such as biologics or targeted synthetic DMARDs, if the treatment target is not achieved with the current combination therapy 1
• Regularly assessing for potential side effects, such as retinal toxicity with Hydroxychloroquine, and taking steps to mitigate these risks 1
• Encouraging a shared decision-making approach between the patient and healthcare provider to determine the best course of treatment 1

Overall, the goal of treatment for patients with overlapping syndrome and Sjögren's syndrome is to achieve remission or low disease activity, while minimizing the risk of side effects and improving quality of life. By continuing the combination therapy with Leflunomide and Hydroxychloroquine, and regularly monitoring for efficacy and side effects, healthcare providers can help patients achieve these goals.

From the Research

Treatment Approach for Overlapping Syndrome and Sjögren's Syndrome

• The treatment approach for a patient with overlapping syndrome and Sjögren's syndrome being treated with Leflunomide and Plaquenil (Hydroxychloroquine) involves a combination therapy of these two drugs, which has been shown to be effective in reducing disease activity and improving symptoms 2, 3.
• The combination of Leflunomide and Hydroxychloroquine has been found to have an additive immunosuppressive effect, which supports the rationale for combination therapy in Sjögren's syndrome 3.
• Studies have also shown that this combination therapy targets type I IFN-associated proteins, which are associated with decreased B cell hyperactivity and disease activity 4.

Key Recommendations

• The use of oral disease-modifying antirheumatic drugs, such as Leflunomide, is recommended for inflammatory musculoskeletal pain in patients with Sjögren's syndrome 5.
• Self-care measures and advice regarding exercise are recommended to reduce fatigue in patients with Sjögren's syndrome 5.
• Rituximab may be used in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex 5.

Future Directions

• Future therapies for Sjögren's syndrome should be designed to improve symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits 6.
• Innovative directions involving interactions with neuroscientists and neuropsychiatrists, together with new immune targeting, may hold promise for better treating Sjögren's syndrome 6.