Long-Term Safety and Efficacy of Repeated Cycles of RimabotulinumtoxinB in the Treatment of Chronic Sialorrhea: Results of the OPTIMYST Trial

Abstract

Introduction: Botulinum toxin injections into the salivary glands inhibit saliva production by reducing the release of acetylcholine at the parasympathetic nerve terminals within the salivary gland. The phase 3 study reported here assessed the safety, tolerability, and effectiveness of repeated cycles of rimabotulinumtoxinB (RIMA) injections in adults with troublesome sialorrhea.

Methods: In this phase 3, open-label multicenter study, 187 adult participants with troublesome sialorrhea due to Parkinson disease (65.8%), amyotrophic lateral sclerosis (13.9%), and other etiologies (20.3%) received up to 4 cycles of RIMA treatment (3500 U every 11-15 weeks).

Results: Participants (69% male, 31% female; mean age 64.1 years) had sialorrhea for a mean of 3.2 years at baseline with a mean Unstimulated Salivary Flow Rate (USFR) of 0.63 ± 0.49 g/min. During the first treatment cycle, RIMA significantly reduced the mean±standard deviation (SD) USFR from baseline to week 4 by - 0.34 ± 0.37 g/min (p < 0.0001), and efficacy was maintained through week 13 (- 0.14 ± 0.29 g/min; p < 0.0001). Reductions were maintained at subsequent injection cycles 2-4, with mean absolute USFRs at weeks 4 and 13 of each cycle similar to those of cycle 1. Most adverse events (AEs) were mild, and the most commonly reported AEs in each cycle that were considered to be treatment-related were dry mouth (≤ 15.5% participants/cycle) and dental caries (≤ 6.0% participants/cycle).

Conclusion: This study demonstrates that RIMA 3500 U safely reduces saliva production over repeated treatment cycles through 1 year, thereby supporting its utility in the management of troublesome sialorrhea in adults.

Gov identifier: NCT02610868.

Keywords: Amyotrophic lateral sclerosis; Botulinum toxin type B; Drooling; Parkinson’s disease; RimabotulinumtoxinB; Sialorrhea.

Fig. 1

Participant disposition. ^aThe study was stopped once sufficient patients required for safety monitoring (across all ongoing rimabotulinumtoxinB trials) had completed treatment. At the time of study stoppage, no participants remained in cycle 1 and patients currently in cycles 2, 3, and 4 completed the study at the end of their current treatment cycle

Fig. 2

a, b Mean unstimulated salivary flow rate (USFR) over cycles 1–4 (a) and percentage of patients rated ‘much’ or ‘very much’ improved on Clinical Global Impression of Change (CGI-C) (b). a Vertical dashed lines indicate the beginning of each cycle. Asterisks indicate p-values for the a priori-specified statistical tests comparing USFR at weeks 4, 8 (cycle 1 only), and 13 of each cycle to the pre-injection USFR for that cycle. Daggers indicate p-values for post-hoc t-tests comparing USFR at weeks 4 and 13 of cycles 2, 3, and 4 to the pre-injection baseline of cycle 1. Sample sizes for each point are provided below the graph. b The CGI-C rated the change in the participants condition (regarding sialorrhea) relative to pre-injection of the current treatment cycle. Percentages were calculated based on the number of participants at each visit (denominators shown at the base of each bar). Of the overall participant population, 57.6% of participants were rated as “much improved” or “very much improved” at week 8 of cycle 1 (the only cycle that included a week 8 CGI-C assessment). For a and b, cycles 1, 2, 3, and 4 are shown in dark blue, orange, green, and light blue, respectively.