Nocturnal and Morning Akinesia Still Prevalent After Nighttime Add-On Parkinson Medications

Author(s):

Key Takeaways

Add-on PD medications reduce but do not eliminate nocturnal and morning akinesia in patients treated with LCIG.
The study involved 409 patients with advanced PD, with 33.3% using nighttime add-on medications 12 months post-LCIG initiation.
Levodopa was the most common nighttime add-on medication, with dopamine agonists as the second most used.
Sleep disturbances in PD are multifactorial, involving medication side effects, motor symptoms, and co-existing sleep disorders.

In a post hoc analysis of the COSMOS study, 24-hour LCIG infusion led to a reduction in nocturnal and morning akinesia, though many patients continued to rely on nighttime add-on medications.

Alfonso Fasano, MD, PhD

In a new analysis of the COSMOS study (NCT03362879), findings revealed that while add-on Parkinson disease (PD) medications may reduce the prevalence of nocturnal and/or morning akinesia, most patients still experienced these issues. Overall, the study suggests that add-on treatments may not fully address the nocturnal treatment gap seen in patients with PD.¹

COSMOS was a multinational, retrospective and cross-sectional, post-marketing, observational study in patients with advanced PD treated with levodopa-carbidopa intestinal gel (LCIG) in routine practice setting. Presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, held September 27 to October 1, in Philadelphia, Pennsylvania, the new post-hoc analysis assessed nighttime PD medication use and change in nocturnal and/or morning akinesia prevalence from baseline to 12 months after LCIG initiation in patients using add-on PD treatments exclusively at night.

Led by senior author Alfonso Fasano, MD, PhD, a professor of neurology at the University of Toronto, 136 of the 409 enrolled patients (33.3%) received add-on PD medications at nighttime 12 months after LCIG initiation. Over that time, the prevalence of nocturnal and/or morning akinesia decreased from 74.3% before LCIG initiation to 61.0% at the study visit. Before LCIG initiation, patients were intaking 1.5 (SD, 1.2) add-on PD medications per night. Twelve months after LCIG initiation, it was about the same, with 1.3 (SD, 0.7) medications per night.

In the study, levodopa was the most common nighttime add-on medication, with a mean dose of 182.2 (SD, 125.6) mg before LCIG initiation and 177.9 (SD, 111.2) mg 12 months after LCIG initiation. The mean levodopa equivalent daily dose of nighttime add-on PD medications was 156.9 (SD, 183.4) mg before LCIG initiation and 214.0 (SD, 146.5) mg 12 months after LCIG initiation. Behind levodopa, dopamine agonists were the second most commonly used add-on medication, with COMT inhibitors, MAO inhibitors, and NMDA antagonists used quite infrequently.

Nearly 70% and 60% of patients with PD experience nocturnal disturbances and early-morning OFF time, respectively, which suggest suboptimal PD management at night. The etiology of impaired sleep-wake cycle in PD is multifactorial and encompasses medication side effects, nocturnal PD motor symptoms, and presence of co-existent sleep and neuropsychiatric disorders. Sleep disorders in PD include insomnia, REM sleep behavior disorder, sleep disordered breathing, restless legs syndrome, and circadian disruption.

COSMOS, a study investigating the effect of LCIG in reducing polypharmacy for the treatment of advanced PD, was originally published in Movement Disorders in 2021. Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 (±23.2) months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation.

The original study results showed that the use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events (AEs), which occurred in 112 study participants (27.4%), were mostly stoma site infection (2.7%), dyskinesia (2.2%), and device malfunction (2.0%).²

A subgroup analysis of COSMOS was published a year later, in 2022, examining the motor and nonmotor outcomes in patients with PD receiving 24- vs 16-hour LCIG. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. In both groups, OFF time, dyskinesia, and prevalence of most symptoms were all reduced. Investigators observed significant differences in the change from baseline in the severity and frequency of freezing of gait with 24-h LCIG vs 16-h LCIG (P = .011 and P = .038), severity of urinary symptoms (P = .006), and frequency of cognitive impairment (P = .014), with 24-h LCIG vs 16-h LCIG.³

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REFERENCES
1. Gurevich T, O’Sullivan S, Parra J, O’Meara M, Zamudio J, Fasano A. Nocturnal use of add-on medications for Parkinson’s disease: post hoc analysis of the COSMOS study. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 650
2. Fasano A, Gurevich T, Jech R, et al. Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study. Mov Disord. 2021;36(8):1853-1862. doi:10.1002/mds.28596.
3. Kovacs N, Szasz J, Vela-Desojo L, et al. Motor and nonmotor symptoms in patients treated with 24-hour daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS). Parkinsonism & Relat Disord. 2022;105:139-144. doi:10.1016/j.parkreldis.2022.08.002