From the Guidelines
Starting Arava (leflunomide) in a patient with high immunoglobulin levels and low CD3 and CD8 counts is not recommended without a thorough evaluation by a rheumatologist or immunologist due to the potential for worsening immune dysregulation. The abnormal lab values suggest immune dysregulation, which could be worsened by Arava's immunosuppressive effects 1. According to the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis, methotrexate monotherapy is strongly recommended over leflunomide in DMARD-naive patients with moderate-to-high disease activity, with a low certainty of evidence 1.
Before starting treatment, additional testing is recommended, including:
- Complete blood count
- Liver function tests
- Screening for latent infections like tuberculosis and hepatitis Patients with pre-existing immune abnormalities may experience increased risk of serious infections while on Arava. The standard dosing regimen typically involves a loading dose of 100 mg daily for 3 days, followed by maintenance dosing of 10-20 mg daily, but this must be individualized based on the patient's specific condition and lab values. Regular monitoring of blood counts, liver function, and immune parameters is essential during treatment. Alternative medications with different mechanisms of action might be safer options depending on the underlying condition being treated.
From the FDA Drug Label
WARNINGS Immunosuppression Potential/Bone Marrow Suppression Leflunomide is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections.
Medications like leflunomide that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis
High Immunoglobulin and Low CD3 and CD8 Labs: It is not safe to start Arava (leflunomide) Rx in a patient with a high immunoglobulin level and low CD3 and CD8 labs, as this may indicate severe immunodeficiency. The FDA drug label warns against using leflunomide in patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections 2.
- Key Considerations:
- Severe immunodeficiency
- Bone marrow dysplasia
- Severe, uncontrolled infections
- Recommendation: Do not start Arava (leflunomide) Rx in this patient.
From the Research
Leflunomide Safety and Immunoglobulin Levels
- The safety of leflunomide, also known as Arava, has been evaluated in several studies 3, 4, 5.
- A study published in 2011 found that leflunomide-induced interstitial pneumonitis is a significant risk, particularly in patients with pre-existing interstitial pneumonitis 3.
- Another study published in 2013 found that leflunomide is a relatively safe drug with proven efficacy in rheumatoid arthritis management 4.
- High immunoglobulin levels and low CD3 and CD8 levels may indicate an immune system imbalance, but there is no direct evidence to suggest that this is a contraindication for leflunomide therapy 6.
Immunoglobulin and CD3/CD8 Levels
- A study published in 2022 found that COVID-19 patients had reduced levels of CD3+, CD4+, and CD8+ T cells, and increased levels of IgM and IgG antibodies at different stages of infection 6.
- The study suggests that cellular immune responses, including CD3+, CD4+, and CD8+ T cells, play a crucial role in controlling SARS-CoV-2 infection 6.
- However, there is no direct evidence to suggest that high immunoglobulin levels and low CD3 and CD8 levels are a contraindication for leflunomide therapy.
Leflunomide Mechanism of Action
- Leflunomide is a disease-modifying antirheumatic drug that inhibits lymphocyte proliferation by blocking dihydroorotate dehydrogenase (DHODH) 5.
- It has been shown to have antiviral effects in in vitro and/or in vivo experiments, and may be useful in combination therapy with methotrexate for patients refractory to methotrexate alone 7.