Less dyskinesia with Duopa tied to reduced pain, improved life quality

Trial analysis demonstrates 'the clinical burden of troublesome dyskinesia'

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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The easing of dyskinesia — the involuntary movements associated with advanced Parkinson’s disease — seen with use of the approved medication Duopa (levodopa-carbidopa intestinal gel) was tied to reduced pain and improved health-related quality of life among patients following treatment.

That’s according to a new analysis of clinical trial data on Duopa that, researchers say, serve to highlight “the clinical burden of troublesome dyskinesia.”

The data also showed that a longer on time — when symptoms are managed adequately, without dyskinesia — was linked to better overall health and to gains in health-related quality of life, known as HRQoL, and daily activities.

“The results of this analysis … highlight the importance of addressing both motor fluctuations and dyskinesia in [people with Parkinson’s], as they are closely associated with HRQoL … and overall condition,” as well as other meaningful outcomes, the researchers wrote.

Their study, “Dyskinesia and Pain in Advanced Parkinson’s Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study,” was published in the journal Neurology and Therapy.

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In Parkinson’s, nerve cells that make the neurotransmitter dopamine are lost, leading to a drop in the levels of this chemical messenger in the brain and the onset of motor symptoms, such as stiffness and slowness of movement.

Levodopa, a precursor molecule that is converted to dopamine in the brain, is the standard therapy for Parkinson’s. It’s often prescribed with carbidopa, which can slow levodopa’s breakdown. Long-term use of levodopa, however, can induce uncontrollable movements, a condition called dyskinesia.

AbbVie’s Duopa, called Duodopa outside the U.S., is an intestinal gel that combines levodopa and carbidopa to treat people with advanced Parkinson’s disease. The therapy, approved in Europe in 2005 and in the U.S. in 2015, is administered over 16 hours via a tube surgically inserted into the intestines.

After the U.S. approval, AbbVie launched DYSCOVER (NCT02799381), an open-label Phase 3 trial, to test the treatment’s effect on dyskinesia. In an open-label trial, both participants and researchers know what treatments the patients are getting.

The study enrolled 63 patients with advanced Parkinson’s who were experiencing ongoing motor fluctuations and uncontrolled dyskinesia despite receiving an optimal Parkinson’s treatment regimen.

After 12 weeks, or about three months, Duopa significantly outperformed optimized medical treatment (OMT) in lessening dyskinesia, as assessed by the unified dyskinesia rating scale (UDysRS). The treatment also reduced pain and enhanced health-related quality of life, activities of daily living, known as ADL, and patients’ overall condition — called a clinical impression — compared with OMT. DYSCOVER wrapped up in 2019.

An analysis of trial data published last year confirmed Duopa’s effectiveness, showing that one year of treatment led to fast and sustained reductions in motor fluctuations and to improvements in symptom control.

Now this post-hoc analysis, one conducted after a trial is complete, aimed to specifically examine correlations between dyskinesia, pain, and health-related quality of life outcomes before the trial, known as baseline, and after. It combined data from 61 participants, more than half of them (52.5%) female.

In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. [But] improvements in dyskinesia and pain were associated with improvements in HRQoL.

At baseline, higher UDysRS scores, or worse dyskinesia, significantly correlated with more pain, as indicated by higher total scores using the King’s Parkinson’s Pain Scale (KPPS), a validated assessment of various types of Parkinson’s-related pain. Dyskinesia also was significantly associated with pain scores related to motor fluctuations.

By week 12, improvements in dyskinesia over OMT were significantly linked to reduced pain, as measured by lower total and fluctuation-related KPPS scores.

With treatment, reduced pain significantly correlated with an enhanced HRQoL, as indicated by the 8-item Parkinson’s disease questionnaire, and activities of daily living, as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2.

Before and after treatment, the impact of dyskinesia significantly correlated with HRQoL and ADL, as well as with clinicians’ assessment of disease severity, as measured by the clinical global impression of severity (CGI-S).

Finally, longer on times without dyskinesia were significantly tied to improvements in HRQoL, ADL, and clinical impression after 12 weeks of Duopa.

“In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. [But] improvements in dyskinesia and pain were associated with improvements in HRQoL,” the researchers concluded.