RT Journal Article
SR Electronic
T1 Long-term safety and effectiveness of tacrolimus in lupus nephritis patients: 5- year interim post-marketing surveillance study in Japan (TRUST)
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.191008
DO 10.3899/jrheum.191008
A1 Tsutomu Takeuchi
A1 Naoko Wakasugi
A1 Satoshi Uno
A1 Hirofumi Makino
YR 2020
UL http://www.jrheum.org/content/early/2020/04/13/jrheum.191008.abstract
AB 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, non-comparative, observational, post-marketing surveillance study conducted across 275 sites in Japan. Registered LN patients are being 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 (ADRs) included pneumonia (1.1%), herpes zoster (1.0%), cellulitis (1.0%) and diabetes mellitus (1.0%). ADRs 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 ADRs 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 effect 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. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01410747]