When to add low-dose prednisone to a rheumatoid arthritis patient on leflunomide (Disease-Modifying Antirheumatic Drug (DMARD))?

From the Guidelines

Low-dose prednisone should be added to leflunomide therapy in rheumatoid arthritis patients when there is persistent moderate to severe disease activity despite adequate leflunomide treatment, or during disease flares with increased joint pain, swelling, and morning stiffness, as recommended by the most recent guidelines 1. When to add low-dose prednisone to a rheumatoid arthritis patient on leflunomide depends on several factors, including disease activity and the presence of poor prognostic factors.

• The 2020 EULAR recommendations suggest that low-dose glucocorticoids should be considered as part of the initial treatment strategy for up to 6 months, but should be tapered as rapidly as clinically feasible 1.
• The goal of adding prednisone is to use it temporarily until disease control improves, then taper gradually to minimize long-term steroid exposure and associated side effects.
• Patients should be monitored for potential adverse effects including hyperglycemia, hypertension, weight gain, osteoporosis, and increased infection risk when adding prednisone.
• Calcium and vitamin D supplementation should be considered for osteoporosis prevention.
• If disease activity remains uncontrolled despite combination therapy with leflunomide and low-dose prednisone for 3-6 months, escalation to biologic DMARDs or targeted synthetic DMARDs should be considered rather than increasing the prednisone dose long-term, as suggested by the 2020 EULAR recommendations 1. Some key points to consider when adding low-dose prednisone to leflunomide therapy include:
• The dose of prednisone is typically 5-10 mg daily.
• The duration of prednisone treatment should be limited to the shortest duration necessary to achieve disease control.
• Patients should be closely monitored for signs of disease flare or worsening disease activity.
• The presence of poor prognostic factors, such as positive rheumatoid factor or anti-cyclic citrullinated peptide antibodies, bony erosions by radiograph, or extra-articular disease, may influence the decision to add prednisone or escalate to biologic DMARDs 1. However, the most recent and highest quality study, the 2020 EULAR recommendations, should be prioritized when making treatment decisions 1.

From the Research

Adding Low-Dose Prednisone to Leflunomide Treatment

When considering the addition of low-dose prednisone to a rheumatoid arthritis patient's treatment regimen who is already on leflunomide, a Disease-Modifying Antirheumatic Drug (DMARD), several factors come into play.

• Efficacy of Low-Dose Prednisone: Studies have shown that low doses of prednisone (less than 10 mg/day) can effectively control the inflammatory features of rheumatoid arthritis and retard bony damage 2, 3.
• Combination Therapy: The use of low-dose prednisone in combination with other DMARDs, such as leflunomide, may enhance the effects of these drugs without significantly increasing adverse events 4.
• Leflunomide's Mechanism and Efficacy: Leflunomide is an isoxazole-based immunomodulator that inhibits the growth of activated lymphocytes, thereby exerting its disease-modifying effects in rheumatoid arthritis. It has been shown to be effective in improving the signs and symptoms of RA and retarding the progression of disease 5.
• Guidelines for Adding Prednisone: While there are no strict guidelines on when to add low-dose prednisone to leflunomide treatment, the decision is typically based on the patient's response to leflunomide alone and the presence of ongoing inflammatory activity. Studies suggest that low-dose prednisone can be safely added to leflunomide, with monitoring for potential side effects such as osteopenia, which can be mitigated with calcium and vitamin D supplementation 2, 3.
• Dosing Considerations: The dose of prednisone to be added can vary, but typically does not exceed 10 mg/day, often given in daily divided doses. Tapering should be done slowly to minimize side effects 3.
• Long-Term Use: There is evidence to suggest that long-term use of low-dose prednisone (less than 5 mg/day) can be effective and acceptable for many patients with rheumatoid arthritis, with manageable side effects 6.

Key Considerations

• The addition of low-dose prednisone to leflunomide should be considered on a case-by-case basis, taking into account the patient's disease activity, response to leflunomide, and potential for side effects.
• Monitoring for side effects and adjustment of the prednisone dose as necessary are crucial for the safe and effective use of this combination therapy.
• Further clinical trials and long-term observational studies are needed to fully understand the benefits and risks of adding low-dose prednisone to leflunomide treatment in rheumatoid arthritis patients.