What are common complications of immunomodulatory therapy?
• Cyclophosphamide: gonadal failure, hemorrhagic cystitis, infection, bone marrow suppression, and malignancy. Acrolein is an unsaturated aldehyde metabolite of cyclophosphamide that causes urotoxicity. Long-term complications are generally correlated with a higher cumulative dose of cyclophosphamide; thus prior exposure to cyclophosphamide needs to be taken into consideration.
• If possible, prior to initiation of treatment with cyclophosphamide, patients should be counseled regarding the risks of treatment. The following should be considered as well:
• Patients interested in having children should be referred to a fertility specialist for cryopreservation and consideration for gonadotropin-releasing hormone agonists (leuprolide).
• Hepatitis B, hepatitis C, and tuberculosis status should be screened prior to starting therapy (infectious disease consultation may be needed in some patients).
• No specific cancer screening is currently recommended; however, age-appropriate cancer screening should be completed.
• Pneumocystis jiroveci (PJP) prophylaxis is needed once therapy is started.
• Patients started on oral cyclophosphamide should be instructed to take the dose in the morning and maintain adequate hydration (adjusted timing of the dose is needed if the patient works exclusively during evening/night shifts). Mesna (2-mercaptoethane sodium sulfonate) has been shown to reduce risk of cystitis in cancer patients receiving high-dose intravenous (IV) cyclophosphamide or ifosfamide; however, this has not been extensively studied in patients with rheumatologic diseases such as SLE. Thus, the use of Mesna remains nephrologist-dependent.Microscopic hematuria, if present at disease onset, can persist during treatment. New-onset microscopic and/or gross hematuria following cyclophosphamide treatment requires further workup, including urologic consultation.
• MMF: gastrointestinal toxicity, such as early satiety, nausea, and diarrhea. In comparison to cyclophosphamide, MMF treatment does not carry the risk of infertility. However, there remain the risks of bone marrow suppression, infection, and neoplasia. PJP prophylaxis is not routinely given in patients receiving MMF. MMF is associated with birth defects; female patients who may become pregnant must be aware of this and should be on an effective form of birth control.
• High-dose prednisone: sequelae may include cushingoid features, weight gain, cutaneous changes such as striae and acne, hypertension, osteopenia, and exacerbation of peptic ulcer disease. Long-term complications include avascular necrosis and osteopenia.
