What is the appropriate dosing and monitoring for azathioprine in a patient with systemic lupus erythematosus (SLE) already taking Saphnelo (anifrolumab) and hydroxychloroquine?

From the Guidelines

Azathioprine for SLE patients already on Saphnelo (anifrolumab) and hydroxychloroquine should typically be initiated at 1-1.5 mg/kg/day, with a gradual increase to a target dose of 2-2.5 mg/kg/day based on clinical response and tolerability. Prior to starting therapy, patients should undergo TPMT (thiopurine methyltransferase) enzyme activity testing to identify those at risk for severe myelosuppression, as dose adjustments are necessary for patients with intermediate or low TPMT activity, as recommended by recent guidelines 1. Monitoring should include:

• Complete blood counts and liver function tests weekly for the first month,
• Then every 2 weeks for the second and third months,
• And monthly thereafter once stable, as suggested by general clinical practice for immunosuppressive therapy. Renal function should be assessed periodically, considering the potential nephrotoxic effects of some immunosuppressive agents. Therapeutic response to azathioprine may take 2-3 months, so patience is required before determining efficacy. When combining azathioprine with Saphnelo and hydroxychloroquine, clinicians should be vigilant for increased immunosuppression, particularly monitoring for infections, as highlighted in the management of SLE patients with immunosuppressive therapy 1. Patients should be advised to report any signs of infection, unusual bruising or bleeding, or gastrointestinal symptoms promptly. Live vaccines should be avoided during this combination therapy, and sun protection is essential due to potential photosensitivity, as generally recommended for patients on immunosuppressive therapy. The decision to initiate azathioprine in a patient with SLE already on Saphnelo and hydroxychloroquine should be based on a thorough assessment of the patient's disease activity, potential benefits, and risks, considering the latest evidence and guidelines for SLE management 1.

From the Research

Azathioprine Dosing and Monitoring in SLE Patients

• The appropriate dosing of azathioprine in patients with systemic lupus erythematosus (SLE) is not explicitly stated in the provided studies, but it is mentioned that azathioprine is used in combination with steroids for patients with lupus nephritis 2.
• Azathioprine may be given to patients who require a maintenance dose of 15 mg or higher of prednisone and for those who experience recurrent flares 2.
• The study from 2001 suggests that azathioprine is effective for patients with skin lesions, pneumonitis, thrombocytopenia, or hemolytic anemia 2.

Monitoring for Azathioprine in SLE Patients

• Monitoring for azathioprine therapy is crucial to minimize potential toxicity, but the specific monitoring parameters are not mentioned in the provided studies.
• However, it is mentioned that mycophenolate mofetil (MMF) was shown to be superior to azathioprine in decreasing the incidence of treatment failure during maintenance therapy, and therapeutic monitoring of MMF levels may be useful 3.

Combination Therapy with Anifrolumab and Hydroxychloroquine

• Anifrolumab, a biologic agent, has been approved for the treatment of SLE and has beneficial effects on the disease 4.
• Hydroxychloroquine is the standard of care for SLE and has been associated with a significant reduction in mortality 5.
• The use of azathioprine in combination with anifrolumab and hydroxychloroquine may be considered for patients with moderate to severe disease, but the specific dosing and monitoring parameters are not explicitly stated in the provided studies 5, 4.