Tacrolimus safe, effective in lupus nephritis through 5 years
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Tacrolimus maintenance over 5 years is well-tolerated and effective among patients with lupus nephritis, according to data published in The Journal of Rheumatology.
“Tacrolimus, an immunosuppressive macrolide that blocks T cell activation by specifically inhibiting calcineurin, is widely administered following organ transplantation,” Tsutomu Takeuchi, MD, PhD, of the Keio University School of Medicine, in Tokyo, and colleagues wrote. “Tacrolimus therapy is considered as a promising treatment option for LN due to associated improvements in the aberrational activation of T lymphocytes, especially Th subsets in LN.”
“Following several randomized studies evaluating the efficacy and safety of tacrolimus as maintenance treatment for LN, tacrolimus was approved for LN treatment in Japan in 2007, and subsequently in other Asian countries,” they added. “However, data concerning the long-term safety and effectiveness of tacrolimus in LN patients in the real-world clinical setting are lacking.”
To analyze the long-term safety and efficacy of tacrolimus (Prograf, Astellas Pharma) in lupus nephritis in a real-world setting, Takeuchi and colleagues commenced the Study to Evaluate the Safety and Efficacy of Tacrolimus for Lupus Nephritis Under Actual Use Situations (TRUST). Currently ongoing, TRUST is an open-label, non-comparative, observational, post-marketing surveillance study of 1,395 registered patients in 275 sites across Japan.
All participants are to be followed for 10 years, with safety and efficacy assessments at weeks 4, 8, 12 and 28, as well as at 1, 1.5 and 2 years, and annually thereafter. For the current analysis, Takeuchi reported on safety and efficacy data for 5 years of tacrolimus maintenance therapy at the interim cutoff in August 2016. Among these participants, 1,355 received tacrolimus maintenance therapy for lupus nephritis and were able to provide safety data, and were thus included in the analysis.
According to the researchers, the most common serious adverse event was pneumonia, at 1.1%, followed by herpes zoster, cellulitis and diabetes, all at 1% each. Adverse events occurred mainly within the first 28 weeks of tacrolimus treatment, with no marked increase reported during the follow-up period. Risk factors for adverse events linked to the drug included inpatient management, lupus nephritis disease severity, increasing age, abnormal renal or hepatic function, and comorbid or previous disease.
The cumulative rate of progression to renal failure was 0.8% at year 1, and then 6.6% at year 5. Further, cumulative relapse rates were 7.8% and 30.6%, respectively. Urine protein to creatinine ratio, serum anti-dsDNA antibody levels, complement C3 levels, and steroid-sparing effect were all significantly improved from week 4 following treatment initiation (P < .001). There results were sustained over 5 years.
“This real-world study of tacrolimus as maintenance therapy in patients with LN showed that it is well tolerated and effective over 5 years,” Takeuchi and colleagues wrote. “The final report of the ongoing PMS study at 10 years will shed further light on the clinical value and characterization of tacrolimus therapy in LN patients. Comparative studies against other immunosuppressive therapies are also required to determine the clinical utility and role of tacrolimus in this setting.” – by Jason Laday
Disclosures: The researchers report non-financial support from Astellas Pharma. Co-authors Naoko Wakasugi, MSc, and Satoshi Uno, MSc, report being employees of Astellas Pharma.
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