Stalevo May Be More Effective Than Other Medications for Early Parkinson’s, Meta-analysis Shows

Stalevo (levodopa, carbidopa, and entacapone combination therapy) may be more effective but seems to be associated with more side effects than other medications to treat early Parkinson’s disease, researchers report.

The study, “Levodopa/carbidopa/entacapone for the treatment of early Parkinson’s disease: a meta-analysis,” was published in Neurological Sciences.

Levodopa (L-DOPA) is the mainstay treatment for Parkinson’s. As the disease progresses, patients typically need to gradually increase their dosage. Even after that, symptoms sometimes reappear or worsen (“off” periods) due to the dopaminergic therapy’s gradual loss of efficiency. Administration of levodopa in combination with both carbidopa and entacapone (LCE, sold by Novartis as Stalevo) has been shown to lessen symptoms and the number of “off” periods.

Although a large number of studies have investigated the treatment of Parkinson’s motor and non-motor symptoms, “there are still many controversies about the diagnosis and treatment of early [Parkinson’s disease] patients,” the researchers wrote.

In the study, a team led by researchers at University of Electronic Science and Technology of China studied the available data regarding the efficacy and safety of Stalevo in people with early Parkinson’s disease. These patients were identified as having idiopathic (of unknown cause) Parkinson’s, Hoehn and Yahr scale stage 3 or less (indicative of mild symptoms in one or both sides of the body), no motor complications history, no treatment, or limited use (generally less than six months) of anti-Parkinson’s medications.

The researchers searched the records of four biomedical databases up through October 2018. They looked for randomized clinical trials, written in English, that used Stalevo to treat early Parkinson’s.

The team analyzed six randomized clinical trials, which involved 1,983 participants (mean age of 60 to 70 years), with a mean average disease duration of 5.3 years.

The Stalevo group consisted of 983 participants and the control group had 1,000 participants. One study used levodopa/dopa decarboxylase inhibitor/entacapone and the remaining five adopted a levodopa/carbidopa regimen in the control group.

In all studies, treatment duration ranged from six to 134 weeks (about 2.5 years).

The Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Disease Questionnaire (PDQ-39) were used to assess symptom severity and quality of life in four of the analyzed studies. The Clinician Global Impression of Change, which measures the change in a doctor’s global impression relative to the beginning of the study, was used as an outcome measure in two trials.

Stalevo was found to improve patients’ motor and non-motor experiences of daily living as measured by the UPDRS part 1 and 2, respectively.

Nonetheless, investigators did not notice any obvious differences between before and after treatment with Stalevo in the Clinician Global Impression of Change, which, according to the authors, could be explained “by a small amount of included studies.”

Also, when PDQ-39 was used as the outcome measure, Stalevo was found not to be as effective as levodopa-carbidopa alone. One possible reason for this is that using PDQ-39 scores may not be sensitive enough to detect changes in these measures in early Parkinson’s patients.

“LCE therapy also increased the risk of total AEs [adverse events], nausea, diarrhea, dyskinesia, dizziness, urine abnormality, and discontinuation risk when compared with traditional therapy,” the researchers wrote.

Around 80.4% of patients treated with Stalevo experienced side effects, compared with 66.8% of those in the control group. Importantly, patients on Stalevo had nearly three times the risk of developing urine abnormality at some point than controls.

Compared to other Parkinson’s medications, and despite the higher percentage of side effects, Stalevo appears to be more effective in the treatment of early Parkinson’s. Still, the researchers advise that these results should be interpreted carefully as this meta-analysis included only six studies.