Rating Scales Show Gel Improves Daily Living Experience in Parkinson's

A Hungarian study was recently the first to use two new ratings scales to confirm that 1 year of treatment with levodopa/carbidopa (LD/CD) intestinal gel (LCIG) therapy can improve dyskinesia and the experiences of daily living in patients with advanced Parkinson’s disease (PD).

Norbert Kovacs, MD, PhD, (pictured) a tenured professor in the Department of Neurology at the University of Pecs in Hungary, presented the results of this multicenter study during a poster session at the 21^st International Congress of the Parkinson’s Disease and Movement Disorders Society in Vancouver, BC.

“We found out that this product significantly improves the motor and the non-motor aspects of daily living,” Kovacs said. “This means that problems such as anxiety, depression, and fatigue are not so troublesome for the patient.”

As PD progresses, severe fluctuations in motor and non-motor symptoms and troublesome dyskinesia develop as side effects of oral drug therapy. Because of the short half-life of LD, these fluctuations can be controlled only by non-oral therapies that can maintain steady and optimal LD levels in plasma.

LCIG (Duopa in US, Duodopa in Europe) is one such non-oral therapy now in widespread clinical use after its introduction into clinical practice a dozen years ago. This therapy enterally infuses a water-soluble formulation of LD into the body’s primary site of LD absorption, the proximal jejunum, through a percutaneous endoscopic gastrostomy tube with a jejunal extension. The tube is connected to a portable infusion pump that continuously delivers the drug to the intestine.

Although previous studies clearly showed that LCIG produced dramatic improvement in health-related quality of life (HRQoL), study data conflicted on its impact on the experiences of daily living.

However, these studies used the Unified Parkinson’s Disease Rating Scale (UPDRS), in which a Movement Disorders Society Task Force identified several weaknesses in capturing PD-related symptoms and their consequences.

As a result, the task force revised the UPDRS to address these weaknesses and increase its reliability. This revision resulted in a new version of the rating scale, the MDS-UPDRS. Although this scale was first published in 2008, none of the larger studies of LCIG used it to assess therapeutic efficacy.

“It’s not the objective measurement of, for instance, how severe the tremor is,” Kovacs said. “It’s a measurement based on the questionnaires that the patients fill out that have questions about how tremor, fatigue, depression, rigidity, and slowness impair his or her life.”

The patients’ metric for improvement is in quality of life, Kovacs said.

“It’s a patient-reported outcome in 2 parts: the non-motor experiences and the motor experiences of daily living, and how the dyskinesia affects those experiences,” Kovacs said.

Previous studies collected only indirect, patient-diary data on LCIG’s effect on dyskinesia. In contrast with patient diaries, the Unified Dyskinesia Rating Scale (UDysRS) reliably measures all aspects of dyskinesia, including presence of “on” and “off” dyskinesia and its impact on the experiences of daily living, as well as the intensity of dyskinesia experienced and the degree of disability caused by it.

Although a recent study showed the UDysRS is more sensitive in detecting changes in dyskinesia and therapy response than other rating scales, none of the previous LCIG studies used it to detect changes in dyskinesia.

To address the limitations of previous studies, Kovacs and team set out to use the newly developed UDysRS and the more robust revision of the UPDRS, the MDS-UPDRS, to determine whether experiences of daily living improved in patients with advanced PD after 1 year of LCIG treatment.

“None of the previous studies utilized these scales, so they were not able to analyze these symptoms,” Kovacs said. “We were the first to use them to assess how Duodopa improves the disabilities associated with the disease.”

The Hungarian team enrolled 34 consecutive patients with advanced PD who were about to receive LCIG therapy in a prospective, open-label study. They examined patients before starting LCIG therapy and 12 months after its initiation and assessed the impact of PD symptoms and dyskinesia on the experiences of daily living by using the 2 new scales.

As a result, they found that patients’ scores on these scales improved by 20% to 28% after 1 year of LCIG therapy.

Their scores on the Non-motor Experiences of Daily Living part of the MDS-UPDRS decreased 20% from a median of 20 points (interquartile range (IQR), 14—23) to a median of 16 points (IQR, 12–20), (P = 0.044). And their Motor Experience of Daily Living scores decreased 25% from a median of 24 points (IQR, 20–29) to a median of 18 points (IQR, 13–25) (P = 0.025).

In addition, their total UDysRS scores decreased 28% from a median of 47 points (IQR, 36—54) to a median of 34 points (IQR, 21–45) (P = 0.003). And their health related quality of life scores measured by the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) also decreased 24% from a median of 35.4 points (IQR, 26.9–50.3) to a median of 27.0 points (IQR, 21.3–31.4) (P = 0.003).

The Hungarian team concluded that these changes in MDS-UPDRS and UDysRS scores confirmed that 1 year of LCIG therapy can efficiently improve the experiences of daily living in patients with advanced PD.

Kovacs added that although LCIG therapy is used for patients with advanced PD, it might also be beneficial in some patients with earlier stage PD “because we can improve the quality of life and reduce the burden of the disease. It can help the patient preserve social status, continue to work, and avoid social problems.”

“I hope these findings will improve the availability of the treatment because it’s not available in all countries,” Kovacs said. “And because of the expense, some limit how many patients are offered the therapy. But we had a good experience with the Hungarian government. We showed them this data, and they increased the availability of the treatment. So it can help payers to expand the budget for it.”

A full report on the study, “Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson’s disease: An open-label study,” appeared in the April 2017 issue of Parkinsonism and Related Disorders.