Objective. To assess the long-term safety and effectiveness of tacrolimus for treating lupus nephritis (LN) in the real-world clinical setting. Methods. This is an ongoing, open-label, noncomparative, observational, postmarketing surveillance study conducted across 275 sites in Japan. Registered patients with LN were followed for 10 years. Here we report data relating to 5 years of tacrolimus maintenance therapy at the interim data cutoff in August 2016. Results. Of 1395 registered patients, 1355 received tacrolimus maintenance therapy for LN and provided safety data. The most common serious adverse drug reactions (ADR) included pneumonia (1.1%), herpes zoster (1.0%), cellulitis (1.0%), and diabetes mellitus (1.0%). ADR occurred mainly within the first 28 weeks of tacrolimus treatment, and no marked increase was observed during the follow-up period. Subgroup analyses suggested that risk factors for commonly observed ADR associated with tacrolimus included inpatient management, LN disease severity, increasing age, abnormal renal or hepatic function, and comorbid or previous disease. The cumulative rate of progression to renal failure (based on the attending physician's assessment) was 0.8% at Year 1 and 6.6% at Year 5. Cumulative relapse rates were 7.8% and 30.6%, respectively. Urine protein:creatinine ratio, serum anti-dsDNA antibody levels, complement C3 levels, and steroid-sparing effects were all significantly improved from 4 weeks after tacrolimus treatment initiation (P < 0.001) and were sustained over 5 years. Conclusion. Long-term tacrolimus maintenance treatment over 5 years in the real-world clinical setting was well tolerated and effective in a large population of patients with LN (www.ClinicalTrials.gov: NCT01410747).
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