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The trial randomized participants into 4 groups, comparing two dosage strengths of the combination drug (2.5 mg aroxybutynin/75 mg atomoxetine and 5 mg aroxybutynin/75 mg atomoxetine), atomoxetine alone (75 mg), and placebo. Participants were adults with OSA and an apnea-hypopnea index (using the greater than or equal to 4% desaturation criterion for hypopnea; AHI4) of 10 to 45 based on polysomnography. Those using CPAP or other devices were included in the study if they had discontinued use more than 2 weeks before the baseline polysomnogram.

Both doses of the combination therapy showed clinically meaningful improvements over the 1-month period in patients with mild to severe OSA. The AHI4 was reduced from a median of 20.5 to 10.8 with the 2.5/75 mg dose, a 47.1% reduction, and from a median of 19.4 to 9.5 with the 5/75 mg dose, a 42.9% reduction, compared to a decrease from a median of 19.0 to 11.8 with atomoxetine alone (−38.8%) and from a median of 20.1 to 16.3 with placebo (−18.9%). The improvement in AHI4 was seen during both rapid-eye-movement (REM) sleep and non-REM sleep; it was statistically significant in non-REM sleep and in either the supine or lateral positions. Compared to placebo, the hypoxic burden was reduced by 12.7 on the 2.5/75 mg dose and by 16.6 on the 5/75 mg dose of aroxybutynin/atomoxetine. A significant improvement in the PROMIS fatigue score was seen with the smaller dose versus placebo (−3.56) and atomoxetine alone (−3.49). The combination didn't affect total sleep time or sleep latency, but did reduce REM sleep, although the decrease was smaller than that seen in single-night studies, suggesting that the effect on REM sleep may ease over time.

Aroxybutynin/atomoxetine didn't differ significantly from atomoxetine alone in its effect for most respiratory parameters, suggesting that the noradrenergic activity of atomoxetine is the primary reason for its effect on upper airway obstruction. However, atomoxetine alone was more likely to disturb sleep than either dose (23.93 fewer minutes of sleep compared to the 2.5/75 mg dose and 16.09 fewer minutes compared to the 5/75 mg dose). The current study suggests that the optimal dosage of the combination may be 2.5/75 mg; higher doses increase the antimuscarinic side effects. It does not eliminate sleep-disordered breathing, as can occur with CPAP. Its lower effectiveness must be balanced against the lower adherence to CPAP, or the practice of using CPAP only part of the night.

The combination demonstrated meaningful improvements in OSA and was generally well tolerated over the 1-month study period, suggesting that it may be an effective treatment option for some patients. Further study in larger populations for longer durations will help identify those populations who will have the best response to aroxybutynin/atomoxetine treatment. (Schweitzer, P. K., et al. (2023). The combination of aroxybutynin and atomoxetine in the treatment of obstructive sleep apnea (MARIPOSA): A randomized controlled trial. Am J Respir Crit Care Med. Advance online publication. Retrieved October 2023 from https://www.atsjournals.org/doi/10.1164/rccm.202306-1036OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)

Released: October 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

Levodopa–carbidopa intestinal gel provides levodopa, the gold standard treatment for Parkinson disease, in a continuous daytime infusion to patients with advanced Parkinson disease, allowing levodopa levels to be maintained at a constant level within the therapeutic window. This bypasses the usual diminishment of effectiveness of levodopa that occurs as the disease progresses.

DUOGLOBE was conducted in 55 sites in 10 countries. Patients enrolled in the study had no prior exposure to levodopa–carbidopa intestinal gel, a Mini-Mental State Exam score of at least 24, no prior surgery for Parkinson disease, and no current use of subcutaneous apomorphine infusion to treat their Parkinson disease. Dosage was individualized, and other Parkinson medications were permitted at the discretion of the treating practitioner. One-year interim results of the study had indicated significant improvements in motor symptoms (including OFF time and dyskinesia) and nonmotor symptoms (including sleep), health-related quality of life (QOL), and caregiver burden.

The study included 195 patients in the 3-year analysis, 61.5% male, with a mean age of 70.2 years and a mean disease duration of 11.2 years. Mean treatment duration was 923.5 days, with median daily duration of 16 hours. The daily dose of the intestinal gel remained stable from Day 1 (1,241 mg/day) through Month 36 (1,365.4 mg/day). Results of the study have demonstrated beneficial effects on motor symptoms: decrease in OFF time and increase in ON time without troublesome dyskinesia. Mean daily hours spent in the OFF state significantly decreased from baseline and remained decreased through Month 36 (−3.3 hours at Month 36). Significant improvements were seen in other measures: United Dyskinesia Rating Scale total scores were significantly reduced from baseline at all visits through Month 36 (mean reduction in score at month 36: −5.9). The subscore of ON dyskinesia was significantly reduced from baseline through Month 24, above the MCID of −2.1, and the subscore of OFF dystonia was significantly reduced through Month 36, above the MCID of −1.8. These parallel improvements (significant decrease in OFF time coupled with significant improvements in ON dyskinesia) are likely due to the continuous delivery afforded by levodopa–carbidopa intestinal gel. Nonmotor total scores also demonstrated significant, sustained improvements from baseline to Month 36 (mean, −14.3), as did scores on three of the nine subdomains (sleep and fatigue, mean −3.7; GI tract, mean −2.5; and miscellaneous nonmotor symptoms, mean −3.9). Finally, health-related QOL significantly improved through Month 24 (score −6.0 on the 8-item Parkinson Disease Questionnaire) and caregiver burden significantly improved through Month 30 (score of −2.3 on Modified Caregiver Strain index).

Slightly more than half of patients (n = 107) experienced a serious adverse event, with event frequency and type as could be expected in this patient population of advanced age with multiple comorbidities. The most common serious adverse events were falls (n = 8), worsening of Parkinson disease (n = 8), and UTI (n = 7).

These findings contribute to our understanding of long-term management of patients with advanced Parkinson disease. Of particular interest is that improvements above the MCID in OFF time, dyskinesia, nonmotor symptoms, sleep, and health-related QOL were maintained long-term in a population with an otherwise progressive disease.(Chaudhuri, K. R., et al. (2023). Levodopa carbidopa intestinal gel in advanced Parkinson's disease: DUOGLOBE final 3-year results. J Parkinson's Dis, 13(5), 769–783. Retrieved October 2023 from https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd225105)

Released: October 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer