IMPACT OF INJECTION GUIDANCE TECHNIQUES ON THE EFFICACY AND SAFETY OF INCOBOTULINUMTOXINA FOR SIALORRHEA

Objective: SIAXI (NCT02091739), a pivotal double-blind, randomised, placebo-controlled study with an extension period (EP), assessed the efficacy and safety of incobotulinumtoxinA 75 or 100 U in patients with sialorrhea due to Parkinson's disease (PD), atypical parkinsonism, stroke or traumatic brain injury. This subgroup analysis assessed the impact of injection guidance technique. Background: Literature suggests that ultrasound (US) guidance of botulinum neurotoxin injections, especially into the submandibular glands, may be needed to improve efficacy and safety. Methods: Patients were randomized (2:2:1) to incobotulinumtoxinA 75 or 100 U, or placebo, distributed in bilateral parotid and submandibular glands in a single injection cycle (IC) in the main period (MP). All eligible patients completing the MP received three further incobotulinumtoxinA ICs (75 or 100 U; each 16+/-2 weeks) in the EP. Injections were consistently guided by US or anatomical landmarks (AL) at investigators' discretion. Outcomes included unstimulated salivary flow rate (uSFR) and patients' Global Impression of Change Scale (GICS). The incidence of adverse events (AEs) was reported. Results: 184 patients were randomised and received either incobotulinumtoxinA 75 U (n=74) or 100 U (n=74), or placebo (n=36) in the MP; 173 completed the MP and entered the EP. In the MP, injections were guided by US in 56.5% of patients and by AL in 43.5%. Among patients treated with incobotulinumtoxinA in all 4 ICs, with US and AL guidance mean uSFR decreased with 75 U and 100 U from study baseline to 4 weeks post-injection, (mean [SD] change from study baseline to end of study: US, -0.15 [0.20] and -0.17 [0.25]; AL, -0.19 [0.22] and -0.17 [0.20]). Patients' GICS also showed improvement at 4 weeks post-injection with both US and AL guidance. The incidence of AEs over all ICs with incobotulinumtoxinA treatment was similar with US and AL guidance (67.0% and 61.0%). The most frequent treatment-related AEs were dry mouth (10.7% and 6.5%) and dysphagia (3.9% and 2.6%). No new safety concerns with respect to guidance technique were reported. Conclusions: In contrast to current literature, repeated incobotulinumtoxinA injections under either US or AL guidance are similarly effective and well tolerated for sialorrhea in patients with PD or other neurological disorders.