Is it safe to restart leflunomide (disease-modifying antirheumatic drug) after treating an infection?

From the Guidelines

Restarting leflunomide after treating an infection should be done cautiously and only after the infection has completely resolved, as recommended by the 2022 American College of Rheumatology guideline 1. Generally, it is safe to resume leflunomide therapy once you are infection-free and have completed your full course of antibiotics or antiviral medications. Before restarting, consult with your rheumatologist who may want to confirm the infection is cleared through follow-up testing or examination. When resuming leflunomide, you typically return to your previous dose rather than requiring a gradual reintroduction. However, if you've been off the medication for an extended period (several weeks or more), your doctor might recommend laboratory monitoring including complete blood count, liver function tests, and possibly kidney function tests within 2-4 weeks after restarting, as suggested by the joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics 1. The caution with leflunomide during infections stems from its immunosuppressive properties, which work by inhibiting pyrimidine synthesis and reducing inflammatory T-cell activity, as noted in the American College of Rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic 1. This mechanism helps control autoimmune conditions but can simultaneously impair your body's ability to fight infections. If you experience any signs of recurring infection after restarting leflunomide (fever, chills, increased pain, redness, or drainage), contact your healthcare provider immediately as you may need to discontinue the medication again until the infection is fully controlled. Some key considerations for restarting leflunomide include:

• The presence of febrile illness, especially illness requiring antibiotic treatment, which may necessitate temporary discontinuation of therapy 1.
• The necessity of repeating loading doses upon restarting administration of the medication, which depends on disease severity and the number of doses missed 1.
• The potential for cardiotoxicity, particularly in the context of COVID-19 and the receipt of other QT-prolonging agents, which may require cardiac monitoring 1. It is essential to follow the guidance of your healthcare provider and the recommendations of relevant guidelines, such as those from the American College of Rheumatology, to ensure safe and effective management of your condition.

From the FDA Drug Label

In the event that a serious infection occurs, it may be necessary to interrupt therapy with leflunomide and administer cholestyramine or charcoal Leflunomide is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections.

The decision to restart leflunomide after treating an infection should be made with caution.

• Key considerations:
  • The infection must be fully treated and under control.
  • The patient's immune system should be assessed to ensure it is not severely compromised.
  • Close monitoring of the patient's condition, including hematologic and liver function tests, is necessary after restarting leflunomide. It is essential to weigh the benefits of restarting leflunomide against the potential risks, particularly the risk of severe infections or bone marrow suppression 2.

From the Research

Safety of Restarting Leflunomide After Treating an Infection

• The decision to restart leflunomide after treating an infection should be made with caution, considering the potential risks and benefits of the medication 3, 4.
• Studies have shown that leflunomide may be associated with an increased risk of infections, particularly in patients with severe disease and those taking concomitant medications such as methotrexate and corticosteroids 4.
• However, leflunomide has also been shown to have antiviral effects, which may be beneficial in certain situations, such as in the treatment of cytomegalovirus infection in lung transplant recipients 5, 6, 7.
• In general, the use of leflunomide should be carefully monitored, and patients should be closely watched for signs of infection or other adverse effects 3, 4.
• The incidence of severe infections in patients taking leflunomide has been reported to be around 3.30/100 patient-years, with patients at increased risk being those with severe disease and taking concomitant medications such as methotrexate and corticosteroids 4.

Considerations for Restarting Leflunomide

• Before restarting leflunomide, patients should be assessed for any underlying infections or other health issues that may be exacerbated by the medication 3, 4.
• The benefits of restarting leflunomide should be weighed against the potential risks, and alternative treatments should be considered if necessary 3, 4.
• Patients should be closely monitored for signs of infection or other adverse effects after restarting leflunomide, and the medication should be discontinued if any serious adverse effects occur 3, 4.