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Real world experience of carglumic acid for methylmalonic and propionic acidurias: the second interim analysis of the multicentre observational PROTECT study
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DOI：10.1186/s13023-026-04522-z.png)
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Abstract
En 中文
Propionic aciduria (PA) and methylmalonic aciduria (MMA) are rare inherited metabolic disorders marked by recurrent metabolic decompensation and hyperammonaemia, resulting in neurological morbidity, chronic complications, and substantial healthcare burden. Although carglumic acid (Carbaglu®) is established for acute hyperammonaemic crises, evidence for its long-term use is limited. This study reports the 18-month interim analysis of PROTECT, a large prospective observational study evaluating chronic Carbaglu® therapy in PA and MMA. PROTECT is a prospective, longitudinal, observational study conducted across 34 centres in seven European countries. Patients with PA or MMA receiving long-term Carbaglu® for at least six months were eligible. Clinical data were extracted from medical records and analysed descriptively. Annualised pre- and post-treatment comparisons were performed in patients with at least six months of life without long-term Carbaglu® prior to initiation. Outcomes included metabolic decompensation events, ammonia control, healthcare utilisation, and growth parameters. Fifty-eight patients were included in this interim analysis. Among 39 evaluable patients, long-term Carbaglu® treatment was associated with reduced annualised metabolic decompensation events, including hyperammonaemic episodes. Mean peak ammonia levels during decompensations and background ammonia concentrations were significantly lower following treatment initiation. Healthcare utilisation decreased substantially, with significant reductions in inpatient admissions, inpatient days, and emergency room visits. Growth parameters remained stable in patients initiating treatment later in life, while patients treated from birth demonstrated sustained metabolic stability and favourable growth profiles. Despite heterogeneity and limitations inherent to real-world observational data, these findings indicate clinically meaningful improvements in metabolic control and healthcare burden with long-term Carbaglu® therapy. Reductions in both acute and background ammonia exposure suggest potential cumulative neuroprotective benefits. This 18-month interim analysis supports Carbaglu® as a beneficial long-term treatment option for patients with PA and MMA, with particular promise when initiated early in life. Ongoing follow-up will further clarify long-term outcomes and inform optimisation of chronic management strategies. Findings based on clinical trial NCT04176523 titled the PRospective Observational study of long-TErm Carbaglu® for the Treatment of PA & MMA (PROTECT), registered retrospectively at ClinicalTrials.gov on 25th November 2019, available at https://clinicaltrials.gov/study/NCT04176523.
Keywords:
Propionic aciduria
Methylmalonic aciduria
Carglumic acid (Carbaglu®)
Long-term treatment
Hyperammonaemia
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