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

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.