Combination Therapy Shown to Reduce Risk of Lower Urinary Tract Infection in Patients With Parkinson Disease

The combination therapy of levodopa and benserazide was associated with a significantly reduced risk of lower urinary tract infections, particularly among women, when compared with another Parkinson disease combination therapy of levodopa and carbidopa.

A combination therapy for Parkinson disease (PD) may reduce risk of lower urinary tract infections (LUTI), a leading cause of hospitalizations, morbidity, and mortality in patients with PD. Study findings were published in the Journal of Clinical Medicine.

Autonomic dysfunctions, including orthostatic hypotension, fatigue, and urinary dysfunction, affect up to 70% of patients with PD and become more prevalent during the course of the disease.

Urinary dysfunction in particular can significantly reduce patients’ quality of life, in which multiple factors can increase the risk of LUTI, such as altered urodynamics, and in patients with PD-related dementia, frailty and diminished cognitive reserve.

“It is hypothesized that in patients with PD, the depletion of dopaminergic neurons in the substantia nigra in parallel with the loss of ventral tegmental area mesolimbic dopaminergic fibers impairs neurogenic bladder control, leading to severe bladder dysfunctions,” explained the study authors.

Several studies have analyzed the impact of dopaminergic drugs on urinary dysfunctions with conflicting results, they added. “However, there is no evidence in the literature of any connection with the occurrence of LUTI when comparing the most commonly used antiparkinsonian medications.”

Levodopa in combination with decarboxylase inhibitors (DCI), such as carbidopa or benserazide, are central substances in the treatment of both PD and restless leg syndrome (RLS), with no significant difference observed in therapeutic effects or adverse reactions between the 2 combination therapies (levodopa/carbidopa and levodopa/benserazide).

The study authors ​​conducted a retrospective cohort study to analyze the incidence of LUTI and antibiotic drug prescriptions among adult patients aged 18 years and older with an initial prescription of levodopa fixed-dose combinations, levodopa/benserazide and levodopa/carbidopa. Patient data was collected from the Disease Analyzer database (IQVIA) of 1284 general practices in Germany between January 2010 and December 2020 (index date).

Patients treated with levodopa/benserazide and levodopa/carbidopa were matched to each other by propensity scores based on sex, age, and diagnoses documented within 12 months prior to or on the index date, including diabetes, PD, RLS, benign prostate hyperplasia, and urinary incontinence.

The main outcome of the study, incidence of LUTI and antibiotic drug prescription, was examined within 12 months after the index date as a function of levodopa fixed-dose combination therapy. Each patient was followed up from the index date for a period of up to 12 months until the first LUTI diagnosis was documented or study therapy ended.

A total of 6168 patients receiving levodopa (100 mg) and benserazide therapy and 6168 patients receiving levodopa (100 mg) and carbidopa were included in the analysis. The mean age of the study cohort was 76.1 years, 55% of patients were women, 53% had PD, 23% RLS, and no diagnosis for prescription was documented for 24%.

Twelve months after the start of therapy, this cumulative incidence of LUTI diagnosis was 10.6% in patients treated with levodopa/benserazide and 11.9% in patients receiving levodopa/carbidopa. Antibiotic therapy was prescribed in 6.7% of patients receiving levodopa/benserazide and 7.7% of patients treated with levodopa/carbidopa.

Compared with patients receiving levodopa/carbidopa, those with prescription of levodopa/benserazide therapy were significantly and negatively associated with LUTI (HR, 0.82; 95% CI, 0.71-0.95). This association was indicated to be stronger in women (HR, 0.77; 95% CI, 0.65-0.92) vs men (HR, 0.93, not significant), with the strongest association observed in patients with RLS (HR, 0.65; 95% CI, 0.47-0.90).

Limitations of the analysis included the lack of information on external confounding factors (alcohol and tobacco consumption, socioeconomic status, etc), hospital data, and mortality.

“This result has far-reaching clinical consequences, especially for patients with PD with the highest LUTI risk (urological dysfunction, PD-related dementia etc) since a levodopa/benserazide combination should be preferred for such patients,” concluded researchers.

Reference

Gremke N, Griewing S, Printz M, Kostev K, Wagner U, Kalder M. Association between Parkinson’s disease medication and the risk of lower urinary tract infection (LUTI): a retrospective cohort study. J Clin Med. Published online November 29, 2022. doi:10.3390/jcm11237077

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