RimabotulinumtoxinB Proves Safe and Effective for Sialorrhea Treatment

January 20, 2020

Use of rimabotulinumtoxinB (Myobloc; US WorldMeds) result in statistically significant reductions in sialorrhea compared to placebo with both 2500 U and 3500 U doses.

Stuart Isaacson, MD

For the treatment of sialorrhea in adult patients, rimabotulinumtoxinB (Myobloc; US WorldMeds), the first and only approved botulinumtoxin type B agent, has shown itself to be safe, effective, and well-tolerated in new study data.1

The study, which included 187 adults with a minimum unstimulated salivary flow rate (USFR) of 0.2 g/min and a minimum Drooling Frequency and Severity Scale score of 4, assessed 2500 U (n = 63) and 3500 U (n = 64) injections compared to placebo (n = 60) in a parallel, double-blind fashion. It ultimately proved to result in statistically significant reductions in sialorrhea compared to placebo with both doses (effect, —0.30 g/min [95% CI, −0.39 to −0.21]; P <.001 for both).

“This study provides class I evidence that treatment with rimabotulinumtoxinB safely reduced saliva production as early as 1 week after injection,” author Stuart Isaacson, MD, director, Parkinson's Disease and Movement Disorder Center of Boca Raton, and colleagues wrote. “These data support the clinical use of rimabotulinumtoxinB for management of troublesome sialorrhea in adult patients.”

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RimabotulinumtoxinB was approved by the FDA for the treatment of chronic sialorrhea in adults in August 2019, adds to its existing approval for the treatment of cervical dystonia, which it was granted in 2000.2 The presence of sialorrhea is common in a number of neurologic disorders, including amyotrophic lateral sclerosis (ALS), Parkinson disease, stroke, and cerebral palsy, among others. Literature suggests that up to three-quarters of those with Parkinson are impacted by excessive drooling, with many citing it as one of the most bothersome symptoms.3

At the time of its approval, Isaacson expressed in a statement that sialorrhea can be distressing for patients and their caregivers with a significant and negative impact on quality of life. “If left untreated, the pooling of saliva can lead to irritation of the skin around the mouth, oral hygiene complications, speech difficulties, and sleep interruption. In some cases, pooling of saliva can lead to choking and aspiration pneumonia,” he said.4

In this study, 122 patients had Parkinson disease (65.2%), 13 (7.0%) had experienced stroke, 12 had ALS (6.4%), 6 had medication-induced sialorrhea (3.2%), 4 had adult cerebral palsy (2.1%), and 30 had sialorrhea owing to other causes (16.0%).

Treatment with both doses significantly reduced the USFR after 4 weeks, with a mean treatment difference of −0.30 g/min for both doses compared to placebo. The Clinical Global Impression of Change (CGI-C) scores were also significantly improved at week 4 for both treatment the 2500 U group (−1.21; 95% CI, −1.56 to −0.87) and the 3500 U group (−1.14; 95% CI, −1.49 to −0.80) compared to placebo (P&thinsp;<&thinsp;.001 for both).

All told, the benefit was observed as early as 1 week after injection and was maintained over approximately 13 weeks of treatment. After 1 week, the CGI-C scores improved in both the 2500 U dose (−0.38; P&thinsp;=&thinsp;.01) and the 3500 U dose (−0.37; P&thinsp;=&thinsp;.01). By Week 8, those treatment differences were −1.06 and −1.15 vs placebo, respectively (P&thinsp;<&thinsp;.001 for both).

The rimabotulinumtoxinB injections were well tolerated compared with placebo. The most common adverse events (AEs) were self-limited mild to moderate dry mouth, dysphagia, and dental caries. Most patients in each treatment group experienced ≥1 AEs, mostly mild or moderate in intensity. The reported AEs were generally considered treatment-related (2500-U: 54.0% [34 of 63]; 3500 U: 56.3% [36 of 64]; placebo: 20.0% [12 of 60]). Only the serious AEs of moderate aspiration pneumonia that resolved and severe pneumonia were considered to be possibly related to the 3500 U dose.

“In current clinical practice, patients are often treated empirically with anticholinergic therapies, including sublingual atropine drops, oral glycopyrrolate, oral benztropine, and oral or transdermal scopolamine,” Isaacson and colleagues wrote. “However, evidence supporting the use of these medications is limited, and their associated risks, including constipation, bradycardia, cognitive impairment, drowsiness, and urinary retention, can be especially problematic in patients with neurological diseases. The lack of these AEs in this study suggests that RIMA may be preferable as an anti-sialorrhea treatment compared with current oral anticholinergic drugs in people with neurological disorders.”

REFERENCES

1. Isaacson SH, Ondo W, Jackson CE, et al. Safety and Efficacy of RimabotulinumtoxinB for Treatment of Sialorrhea in Adults: A Randomized Clinical Trial. JAMA Neurol. Published online January 13, 2020. doi:10.1001/jamaneurol.2019.4565.

2. Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L. Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial. Mov Disord. 2012;27(2):219-226. doi: 10.1002/mds.23929.

3. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, et al. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease. Movement Disord.2011;26(3):399—406. doi: 10.1002/mds.23462.

4. FDA Approves US WorldMeds' MYOBLOC® (rimabotulinumtoxinB) Injection for Chronic Sialorrhea [press release]. Louisville, KY: US WorldMeds; Published August 26, 2019. biospace.com/article/releases/fda-approves-us-worldmeds-myobloc-rimabotulinumtoxinb-injection-for-chronic-sialorrhea. Accessed January 20, 2020.