Objective: To assess the influence of updated Levodopa Equivalent Daily Dosage (LEDD) conversion factors in capturing the newer therapies in Parkinson’s Disease (PD) and therapy modules in different geographical cohorts.

Background: The new LEDD calculation algorithms help in capturing and harmonization of PD therapies.  Analyzing these updates is essential for validating their effectiveness and refining protocols.

Method: Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al. and Jost et al., alongside investigating demographic disparities.

Results: The analysis involved 2,943 subjects (64% males), primarily from India (38.5%), Canada (36.8%), Bangladesh (8.5%), Sri Lanka(5%), Nepal(4.7%), Thailand(5.9%), and others. 87% (n=2,577) met the UK Brain Bank criteria for Parkinson’s Disease (PD). The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598mg vs 610mg, p<0.0001).(Fig-1)

Geographical disparities highlighted variations in PD onset age, with India presenting the youngest average onset (53.5 years) and Sri Lanka the oldest (61.1 years) (p<0.0001). Jost and Tomlinson’s calculations demonstrated consistency within but significant differences across countries (p<0.0001). (Fig-3,5)

Age at onset (< 21 years, 21-50 years &> 50 years) revealed statistically significant differences in LEDD requirements (p<0.0001), which were particularly higher in 21- 50 years (718mg vs 566mg). This subgroup also demonstrated increased usage of non-Levodopa therapies (p<0.0001). (Fig-2)

Gender-based analysis indicated no significant differences in age at onset or symptom duration. However, men exhibited higher total LEDD (p=0.001). (Fig-4)

34% reported dyskinesia, associated with higher LEDD (756mg, p<0.0001). Surgical surgically treated patients? also had higher LEDD (p<0.0001) and a significant difference between Jost and Tomlinson dosages (761mg vs716mg) reflecting the incorporation of newer therapeutic molecules.

Conclusion: This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age-related, and gender-specific variations, in real-life management scenarios.

LEDD Calculation Methods Comparison

LEDD Comparison- Age at Onset vs Countries

LEDD Comparison – Duration of Symptoms & Countries

LEDD Comparison by Age at Onset and Gender

LEDD Comparison by Duration of Symptoms and Gender

References: 1. Jost ST, Kaldenbach MA, Antonini A, Martinez-Martin P, Timmermann L, Odin P, Katzenschlager R, Borgohain R, Fasano A, Stocchi F, Hattori N, Kukkle PL, Rodríguez-Violante M, Falup-Pecurariu C, Schade S, Petry-Schmelzer JN, Metta V, Weintraub D, Deuschl G, Espay AJ, Tan EK, Bhidayasiri R, Fung VSC, Cardoso F, Trenkwalder C, Jenner P, Ray Chaudhuri K, Dafsari HS; International Parkinson and Movement Disorders Society Non-Motor Parkinson Disease Study Group. Levodopa Dose Equivalency in Parkinson’s Disease: Updated Systematic Review and Proposals. Mov Disord. 2023 Jul;38(7):1236-1252. doi: 10.1002/mds.29410. Epub 2023 May 5. PMID: 37147135.
2. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord. 2010 Nov 15;25(15):2649-53. doi: 10.1002/mds.23429. PMID: 21069833.

Acknowledgement :
We acknowledge the contribution of the Canadian Data through Canadian Open Parkinson Network (C-OPN) (https://copn-rpco.ca/). This project has been made possible by Brain Canada through the Canada Brain Research Fund, with financial support of Health Canada and Parkinson Canada.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/real-world-multicenter-analysis-of-levodopa-equivalent-daily-dosage-algorithms-capturing-geographical-and-demographic-disparities-in-parkinsons-disease-therapy-spanning-six-countries-and-two-contin/