Long-term safety and effectiveness of tacrolimus in patients with lupus nephritis in Japan: 10-year analysis of the real-world TRUST study.

OBJECTIVE: To assess the long-term safety and effectiveness of tacrolimus as maintenance therapy in patients with lupus nephritis (LN) receiving treatment in real-world clinical settings in Japan.

METHODS: An open-label, non-comparative, observational, prospective post-marketing surveillance study was conducted in 1395 patients with LN receiving maintenance treatment with tacrolimus at 278 medical institutions across Japan over a period of 10 years. Tacrolimus continuation rate and cumulative incidence of adverse drug reactions (ADRs), relapse, progression to renal failure and progression to dialysis were calculated using Kaplan-Meier analysis.

RESULTS: Safety data were available for 1355 patients, almost half (49.3%) of whom remained on tacrolimus for the full 10 years of follow-up. A significant reduction in mean (SD) daily oral corticosteroid dose was observed from 16.0 (9.7) mg/day at 4 weeks after initiation of tacrolimus treatment to 7.2 (4.4) mg/day at Year 10 (p<0.001). The most frequently reported serious ADRs were infections (reported for 131 patients, [9.7%]). Except for infections, no marked increase in the incidence of any other ADRs was seen over time, including renal impairment, malignant tumors, and cardiac dysfunction. Renal function was generally well-maintained over the 10 years of follow-up. At Year 10, cumulative rates of relapse, renal failure and dialysis were 44.5%, 12.2% and 4.5%, respectively.

CONCLUSION: Tacrolimus was effective and generally well-tolerated as maintenance therapy for LN in a large cohort of patients in Japan followed for 10 years; almost half of whom remained on therapy for the entire duration of follow-up (www.

CLINICALTRIALS: gov: NCT01410747).