• Mode of administration of CYC depends on the clinical scenario and clinical judgment.
• The two commonly recommended IV regimens are:
High dose: Monthly boluses of 0.5–1.0 g/m 2 IV × 6 months
Low dose (Euro-Lupus protocol): 500 mg IV every 2 weeks × 6 doses
• Low-dose therapy is associated with fewer serious infections and less risk of infertility, but some patients may fail to respond to lower doses
• IV dosing regimens (compared with oral) result in a lower total CYC exposure, which is important when considering effects on fertility and bladder toxicity.
• Note that the risk of premature ovarian failure correlates with the cumulative dose of CYC (>10–15 g total dose) and the age of the patient (>30 years).
• Measurement of anti-Mullerian hormone assesses ovarian reserve can be considered but clinical utility is unclear
• For recalcitrant disease, consider rituximab 1 g with CYC 500–750 mg IV followed by the same 14 days later. Response may take months. The CALIBRATE study is investigating this regimen followed by belimumab for Class III/IV nephritis, but the results were not as promising as hoped.