VANCOUVER, BC—IncobotulinumtoxinA injections customized by site and dose improved hand and forearm tremor symptoms patients with Parkinson’s disease without increasing hand weakness, results from the first randomized, placebo-controlled trial presented at the 68th AAN Annual Meeting reported.
Hand weakness was 6.5% in this study, compared with 30% or more reported in studies of essential tremor, Shivam Om Mittal, MD, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, told meeting attendees.
Rest tremor, the most common presenting symptom of Parkinson’s disease, is observed in up to 74% of patients, significantly affecting quality of life in about one-third and debilitating due to psychosocial distress in about one-quarter, he said.
“Among all motor symptoms, it is the least responsive to dopamine therapy,” he added.
Previously, results of three open-label studies suggested some benefit from botulinum toxin in tremor; however, no blinded studies have been done.
To determine whether “a flexible, customized approach” may show better results, “particularly in terms of reducing hand weakness,” Dr. Mittal and colleagues conducted a randomized, double-blind, placebo-controlled cross-over study of incobotulinumtoxinA at the Yale Movement Disorder Center, New Haven, CT.
Participants included those with Parkinson’s disease with moderate to severe tremor. During the study, no existing medications and/or nonpharmacological treatments were changed. Mean age was 65 years; 23 were male and 7, female. The average years of symptoms of Parkinson’s disease was 6.2 years and years of diagnosis, 5.1 years.
A total of 30 patients were assessed with dynamometric hand-strength evaluation and clinical rating scales at 4, 8, and 12 weeks after the injection: The Unified Parkinson’s Disease Rating Scale (UPDRS) tremor questions, the primary study objective, and the NIH Collaborative Genetic Tremor Severity Score (NIHCG), the Patient Global Impression of Change (PGIC), and the Parkinson’s Disease Quality of Life Questionnaire (PDQL), all secondary study objectives.
The injection group received incobotulinumtoxinA mixed with normal saline, a dilution of 10U per 0.1mL (n=15). The placebo group received normal saline at the same volume (n=15). Injection sites, guided by electromyography (EMG) tremor-related activity and determined by the movement disorder specialist, comprised 10 to 12 muscles in the hand, forearm, and arm. Total dose ranged from 80U to 100U/session.
Results showed that change in UPDRS tremor scale was significant at 4, 8, and 12 weeks (P=0.001). Changes in NIHCG and PGIC scores were also significant at all time points (P=0.001); however, change in PDQL scores was not significant at either 4 weeks (P=0.058) or 8 weeks (P=0.042).
Grip strength, using an accelerometer at 4 weeks after injection, showed nonsignificant weakness (P=0.57).
Dr. Mittal acknowledged that study limitations include the small sample size, and recommended that Phase 3 trials with larger samples should be done in the future.
The investigator-initiated study was funded by Merz Pharmaceuticals.