Efficacy and safety of Nitisinone for patients with alkaptonuria: A systematic review with metanalysis

IF 3.5 2区生物学 Q2 ENDOCRINOLOGY & METABOLISM Molecular genetics and metabolism Pub Date : 2025-03-26 DOI:10.1016/j.ymgme.2025.109099

Flávia Diniz Mayrink , Gilson Dorneles , Igor Martins da Silva , Camila Alves Areda

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Abstract

Aim

We conducted a systematic review to assess the efficacy and safety of nitisinone for the treatment of patients with alkaptonuria (AKU).

Methods

Randomized clinical trials that assessed the impact of nitisinone on urinary and serum homogentisic acid (HGA), quality of life, joint range of motion, and adverse events in AKU patients were retrieved from Pubmed and EMBASE up to May 2024. Risk of bias assessment was performed with RoB 2.0, and the GRADE approach assessed the certainty of evidence (CoE) of each main outcome.

Results

Four publications from three studies summarizing data of 218 patients with AKU were included in the review process. Nitisinone administration decreased the urinary HGA levels (mean difference [MD]: −38.98; 95 % confidence interval [95 %-CI]: −53.18 to −24.78; CoE: moderate) without changes in the range of motion of the worst hip joint (MD: -6.23; 95 %-CI: −13.91 to 1.44; CoE: High). On the other hand, large increases in tyrosine were observed associated with nitisinone treatment (MD: 708.77; 95 %-CI: 649.32 to 768.22; CoE: High). AKU patients treated with nitisinone presented increased general health perception (MD: 2.77; 95 %-CI: 0.62 to 4.91), mental health (MD: 1.03; 95 %-CI: 0.90 to 1.19) and mental role functioning (MD: 5.57; 95 %-CI: 0.47 to 10.66). No statistical increases in overall adverse events (Relative Risk [RR]: 1.03; 95 %-CI: 0.90 to 1.19; CoE: High) or serious adverse events (RR: 2.47; 95 %-CI: 0.24 to 25.91; CoE: low) were observed.

Conclusion

This systematic review identified significant potential for nitisinone to modify the natural history of AKU, considering the relevance of clinical changes induced by the treatment.

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尼替西酮治疗尿尿患者的疗效和安全性：一项荟萃分析的系统评价

AimWe进行了一项系统评价，以评估nitisinone治疗alkaptonuria （AKU）患者的有效性和安全性。方法从Pubmed和EMBASE检索截至2024年5月的随机临床试验，评估尼替西酮对AKU患者尿和血清均质酸（HGA）、生活质量、关节活动范围和不良事件的影响。采用RoB 2.0进行偏倚风险评估，GRADE方法评估每个主要结局的证据确定性（CoE）。结果综述过程中纳入了来自3项研究的4篇出版物，总结了218例AKU患者的数据。尼替西酮降低尿HGA水平(平均差值[MD]:−38.98；95%置信区间[95% -CI]:−53.18 ~−24.78；CoE：中度)，没有改变最差髋关节的活动范围(MD: -6.23；95% -CI:−13.91 ~ 1.44；CoE:高)。另一方面，酪氨酸的大量增加与尼替西酮治疗相关(MD: 708.77；95% -CI: 649.32 - 768.22；CoE:高)。接受尼替西酮治疗的AKU患者总体健康知觉增加(MD: 2.77；95% -CI: 0.62 - 4.91)，心理健康(MD: 1.03；95% -CI: 0.90 - 1.19)和心理角色功能(MD: 5.57；95% -CI: 0.47至10.66)。总体不良事件无统计学增加(相对危险度[RR]: 1.03；95% -CI: 0.90 ~ 1.19；CoE：高)或严重不良事件(RR: 2.47；95% -CI: 0.24 ~ 25.91；CoE：低)。结论考虑到治疗引起的临床变化的相关性，本系统评价发现尼替西酮具有显著的改变AKU自然史的潜力。

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来源期刊

Molecular genetics and metabolism 生物-生化与分子生物学

CiteScore

5.90

自引率

7.90%

发文量

621

审稿时长

34 days

期刊介绍： Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.