1. Deferiprone was associated with an increase in MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores compared to placebo, indicating worsening symptoms.
2. The deferiprone group had faster disease progression and more adverse events than the placebo group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Parkinson’s disease is characterized by a loss of dopaminergic neurons in the substantia nigra leading to cognitive and motor symptoms. Deferiprone is an iron chelator that reduces iron accumulation which may be implicated in the pathophysiology of neuronal death. The present study aimed to assess the effect of deferiprone on Parkinson’s symptoms. MDS-UPDRS scores were significantly increased (symptoms worsened) from baseline to week 36 in the deferiprone group compared to the placebo group. Between-group differences were observed for MDS-UPDRS scores and the Parkinson’s Disease Questionnaire (PDQ-39), with worse outcomes in the deferiprone group than the placebo group. The stand-walk-sit test and the Montreal Cognitive Assessment (MoCA) yielded similar results in both groups. After a four-week washout period, the primary and secondary outcome measures were similar between groups. Left and right putamen and right caudate nucleus volumes decreased in the placebo group but increased with the deferiprone group. Psychiatric disorders were more frequently reported with deferiprone than with placebo. A greater percentage of participants in the deferiprone group had progression of Parkinson’s disease than placebo. A limitation of this study was the high dropout rate, particularly in the deferiprone group.
Click to read the study in NEJM
Relevant Reading: A double-blind, delayed-start trial of Rasagiline in Parkinson’s disease
In-Depth [randomized controlled trial]: This phase two randomized, placebo-controlled trial examined the efficacy and safety of deferiprone in patients with newly diagnosed Parkinson’s disease who had not been treated with dopaminergic drugs. Participants had to have been diagnosed less than 18 months earlier and report mild symptoms so they could complete a nine-month trial without symptomatic treatment. Participants received 600mg of delayed-release deferiprone at a dose of 15mg per kilogram twice daily or a matching oral placebo twice daily for 36 weeks, followed by a four-week washout period. The mean MDS-UPDRS increased by 15.6 points in the deferiprone group compared to 6.3 points in the placebo group (95% Confidence Interval [CI], 6.3 to 12.2; p<0.001). The change in MDS-UPDRS part III was 9.8 points in the deferiprone group compared to 4.0 in the placebo group (95% CI, 3.8 to 7.7). The change in MDS-UPDRS part II was 4.2 points in the deferiprone group compared to 1.8 in the placebo group (95% CI, 1.3 to 3.6). The difference in the sum of MDS-UPDRS part II and part III scores in the deferiprone group was 14.2 compared to 5.9 in the placebo group (95% CI, 5.7 to 10.8). A total of 22.6% of participants in the deferiprone group and 2.7% of the placebo group had to discontinue the study due to disease progression. In summary, the present study suggests that deferiprone is unsuitable for treating Parkinson’s disease.
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