Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

Abstract

BACKGROUND:

Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study.

METHODS:

In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation.

RESULTS:

Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences.

CONCLUSIONS:

Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

• Authors: Ho Jun Chin, Dong-Wan Chae, Yong Chul Kim, Won Suk An, ChunGyoo Ihm, Dong-Chan Jin, Sung Gyun Kim, Yong-Lim Kim, Yong-Soo Kim, Yoon-Goo Kim, Ho Seok Koo, Jung Eun Lee, Kang Wook Lee, Jieun Oh, Jung Hwan Park, Hongsi Jiang, Hyuncheol Lee, Sang Koo Lee
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 32 Issue 1 Pg. 199-210 (01 2021) ISSN: 1533-3450 [Electronic] United States
• PMID: 33168602 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2021 by the American Society of Nephrology.

Chemical References

• Adrenal Cortex Hormones
• Immunosuppressive Agents
• Prednisolone
• Tacrolimus

Topics

• Adolescent
• Adrenal Cortex Hormones (administration & dosage)
• Adult
• Aged
• Drug Administration Schedule
• Humans
• Immunosuppressive Agents (therapeutic use)
• Medication Adherence
• Middle Aged
• Nephrosis, Lipoid (drug therapy)
• Patient Safety
• Prednisolone (therapeutic use)
• Recurrence
• Remission Induction
• Republic of Korea
• Tacrolimus (administration & dosage)
• Treatment Outcome
• Young Adult