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Real-world long-term safety and efficacy of tacrolimus: Final analysis of the TRUST study

By Haimanti Mandal

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Mar 14, 2024

Learning objective: After reading this article, learners will be able to cite a new clinical development in systemic lupus erythematosus.


Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus that contributes to increased morbidity and mortality. Tacrolimus, a calcineurin inhibitor, is approved in Japan and other Asian countries for the treatment of LN. However, there is a lack of robust data on its long-term safety and efficacy as a maintenance therapy in LN.

Here, we summarize an article published by Takeuchi et al. in The Journal of Rheumatology that assessed the 10-year safety and efficacy of tacrolimus as maintenance therapy in Japanese patients with LN treated in real-world clinical practice.1

Methods1

  • TRUST was a 10-year, open-label, observational, non-comparative, post-marketing surveillance study (NCT01410747) conducted across 278 sites in Japan.
  • Kaplan–Meier analysis was used to calculate tacrolimus continuation rate, cumulative incidence of adverse drug reactions (ADRs), relapse, and progression to renal failure and dialysis.

Key findings1

  • A total of 1,355 and 1,353 patients were included in the safety and efficacy analysis sets, respectively.
    • The mean age of patients was 38.3 years and 84.9% were women.

Treatment

  • Over the 10-years of follow-up, the tacrolimus continuation rate was 49.3%. The most common reasons for treatment discontinuation were onset of adverse events (17.9%), unchanged/worsened symptoms (14.8%), symptoms improved (4.1%), and patient requests (4.8%).
  • In the 94.6% of patients receiving corticosteroids at baseline, the mean prednisolone equivalent daily dose of oral corticosteroids reduced significantly from Week 4 (16 mg/day) to Year 10 (7.2 mg/day; p < 0.001).

Safety

  • Over 10 years, 2,409 ADRs were reported in 60.6% of patients (Figure 1).
    • The most commonly reported ADRs were hypertension (7.7%), nasopharyngitis (5.4%), herpes zoster and diarrhea (both 4.6%), upper respiratory tract inflammation (4.1%), bronchitis (3.8%), increased blood creatinine (3.7%), hyperuricemia (3.2%), diabetes mellitus (3.1%), pharyngitis (3.0%), gastroenteritis and renal impairment (both 2.9%), cystitis (2.4%), constipation (2.3%), and pneumonia (2.1%).
  • The most frequently reported serious ADRs were infections (Figure 1).
  • There was no marked increase in incidence of any ADR or serious ADR over time.
  • Overall, 48 patients (3.5%) died over the 10 years of follow-up.

Figure 1. Incidence of ADRs and serious ADRs over 10 years of follow-up*

ADR, adverse drug reaction.

*Data from Takeuchi, et al.1

 

Efficacy

  • In the efficacy analysis set (n = 1,353), the cumulative rate of relapse was 44.5% at 10 years.
  • In the renal prognosis analysis set (n = 1,140), the cumulative rates of progression to renal failure and dialysis were 12.2% and 4.5%, respectively, at 10 years.
  • Serum creatinine levels were relatively consistent from Year 1 through Year 10.
  • The estimated glomerular filtration rate at baseline (80.9 mL/min/1.73 m2) decreased significantly from Week 4 (79.3 mL/min/1.73 m2) to Year 10 (68.3 mL/min/1.73 m2; p < 0.001).

Key learnings

  • Tacrolimus was effective and well tolerated as a maintenance therapy in Japanese patients with LN after 10 years of follow-up.
  • However, it is worth noting that data may not reflect recent changes in the LN treatment landscape, such as the approval of belimumab in Japan.
  • Nevertheless, the findings reinforce the use of tacrolimus in the clinical management of patients with LN.

References

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