Impact of Dosing Strategy on Clinical Outcomes of Patients with Lupus Nephritis Initially Treated with Lower-Than-recommended-dose Cyclophosphamide

Aim Cyclophosphamide is the mainstay treatment for patients with lupus nephritis (LN); it can be prescribed at lower doses than the recommended regimen to avoid side effects. We aimed to investigate the impact of cyclophosphamide dosing strategies on treatment outcomes of patients with LN initially treated with a lower-than-recommended dose. Methods We retrospectively reviewed patients with proliferative LN (class III, IV, or mixed) initially treated with lower-than-recommended-dose cyclophosphamide. Patients who received a titrated dose of cyclophosphamide ≥0.5 g/m2 were categorized into the titrate group, while those who received doses <0.5 g/m2 were categorized into the non-titrate group. The primary outcome was primary renal response (PRR) at 52 weeks. Results Of the 78 patients included, 47 were assigned to the titrate group and 31 to the non-titrate group. The titrate group had a higher proportion of PRR achievement (23 of 47 patients [48.9%] vs. 7 of 31 patients [22.6%] in the non-titrate group). After adjusting for potential confounders, a baseline urinary protein-to-creatinine ratio ≥3 g/g (OR, 0.3; 95% CI, 0.1–0.9; P=0.030), and titrating the dose of cyclophosphamide to ≥0.5 g/m2 (OR, 4.7; 95% CI, 1.5–15.2; P=0.010) were independent factors for PRR. Additionally, the titrate group had a lower rate of infection (8 of 47 patients [17.0%] vs. 12 of 31 patients [38.7%], respectively; OR, 0.3; 95% CI, 0.1–0.9; P=0.036) and death associated with LN (4 of 47 patients [8.5%] vs. 8 of 31 patients [25.8%], respectively; OR, 0.3; 95% CI, 0.1–0.9; P=0.047) compared with the non-titrate group. LN flare and the need for rescue therapy did not differ between the groups. Conclusion For patients with LN initially treated with lower-than-recommended-dose cyclophosphamide, titration of the cyclophosphamide dose ≥0.5 g/m2 was beneficial on renal response, while reducing infection leading to hospitalization and LN-associated death.