Recognition, Description, and Variability of Spasticity in Individuals With Multiple Sclerosis and Potential Barriers to Clinician-Patient Dialogue: Results From SEEN-MSS, a Large-Scale, Self-Reported Survey.

BACKGROUND: The experience with spasticity varies among individuals with multiple sclerosis and spasticity (MSS), as they may not recognize it as spasticity or have the language to describe their symptoms. This can lead to potential delays in diagnosis and treatment. METHODS: Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity was an online survey completed by 1177 individuals with MSS in 2021. It sought to capture symptoms of spasticity, variability of symptoms, specific spasticity triggers, and how conversations with physicians were initiated. RESULTS: The mean age of the cohort was 56.8 years and it was 78% women. Prior to spasticity onset, 65% of respondents felt minimally prepared or unprepared for possibly developing spasticity and were unaware that spasticity manifests as part of MS. Eighty percent experienced spasticity daily, which was variable in severity and duration. Spasticity was triggered by a range of factors and 90% of those surveyed were unable to predict when it would occur or its severity. Day-to-day variability of spasticity prevented 65% of respondents from doing things they wished to do. Sixty percent were confused by their symptoms, not recognizing them as spasticity. Although 91% reported experiencing muscle spasms, only 69% used "muscle spasms" to describe their symptoms. Other descriptors included "muscle tightness," "stiffness," "cramping," and "pain." After recognizing spasticity, 78% proactively initiated discussions with their physicians, 52% wished they had done so sooner, and 42% delayed the conversation by up to or more than a year. CONCLUSIONS: Results emphasize the variable nature of spasticity and the lack of a common language to describe symptoms, underscoring the importance of education, earlier recognition, and customized treatments tailored to the severity and duration of spasticity symptoms.

Efficacy of nabiximols oromucosal spray on spasticity in people with multiple sclerosis: Treatment effects on Spasticity Numeric Rating Scale, muscle spasm count, and spastic muscle tone in two randomized clinical trials.

BACKGROUND: To provide a comprehensive assessment of the treatment effects of nabiximols oromucosal spray on multiple sclerosis spasticity in two clinical trials, GWSP0604 and SAVANT. METHODS: Both studies enriched for responders before randomization, defined by a ≥20% improvement in Spasticity 0-10 numeric rating scale (NRS) score. Additionally, SAVANT used randomized re-titration following washout. Spasticity NRS outcomes, spasm count, and modified Ashworth scale (MAS) scores were analyzed. RESULTS: Mean change from baseline in average daily Spasticity NRS scores was significantly larger for nabiximols than placebo at all postbaseline timepoints, ranging from -0.36 to -0.89 in GWSP0604 and -0.52 to -1.96 in SAVANT. Percent reduction in geometric mean change from baseline in average daily spasm count for nabiximols ranged from 19-35% versus placebo. A treatment difference favoring nabiximols was observed in overall MAS scores during the randomized part of each study. Treatment effect was larger for combinations of lower limb muscle groups (ranging between -0.16 and -0.37). CONCLUSIONS: Nabiximols leads to improvement in spasticity that was sustained over the 12-week treatment period as measured by average daily Spasticity NRS scores, daily spasm counts, and MAS scores for combinations of muscle groups, especially the combination of the 6 key muscle groups in the lower limbs in NRS responders to nabiximols treatment.

Immunogenicity and long-term efficacy of botulinum toxin type B in the treatment of cervical dystonia: report of 4 prospective, multicenter trials.

OBJECTIVE: Therapeutic botulinum toxins are antigenic proteins with the potential to produce antibodies (Abs). It is, however, unclear whether Abs to Myobloc® (rimabotulinumtoxinB, botulinum toxin type B, BoNT-B) impact the efficacy and safety of BoNT-B treatment of cervical dystonia (CD). The objective was to determine if Abs to BoNT-B impact the efficacy or safety of long-term BoNT-B treatment of CD. METHODS: Four separate prospective clinical trials, with a combined total of 1134 subjects evaluable for immunogenicity over total treatment durations of up to 6+ years, were conducted studying the efficacy, safety, and immunogenicity of BoNT-B treatment of CD. Botulinum toxin type B injections were administered approximately every 3 months. Efficacy was assessed using the Toronto Western Spasmodic Torticollis Rating Scale-Total Score, the Subject Global Assessment, or the Treatment Assessment Scale. The presence of Abs to BoNT-B was assessed using the mouse neutralizing antibody (MNA) assay. Cross-sectional and longitudinal statistical analyses were performed to compare efficacy by MNA status at each time point and over time in Ab-positive individuals before and after seroconversion. Safety was assessed by summarizing adverse events by Ab status. RESULTS: Long-term efficacy was observed with multiple treatments of BoNT-B. Across all 4 studies, there was no correlation between MNA status and rates of clinical response, study withdrawal, or safety profile. CONCLUSIONS: Botulinum toxin type B is effective and safe in the repeat, long-term treatment of CD. The presence of Abs to BoNT-B as detected by the MNA assay does not have any meaningful clinical impact or correlation.

Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial.

Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can significantly impair a patient's health and quality of life. Fifty-four PD subjects with troublesome sialorrhea were enrolled using a multicenter, randomized, double-blind, sequential-dose escalation design in which subjects received a single intraglandular treatment with botulinum toxin type B (doses of 1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo. Postinjection, subjects were followed acutely for 4 weeks and long-term for up to 20 weeks. Safety/tolerability, as assessed by adverse events, was the primary outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal-related adverse events occurred more frequently in the active groups versus placebo group (31% vs 7%), with dry mouth being most common (15%). There were no serious adverse events attributed to botulinum toxin type B or discontinuations due to adverse events from treatment. At 4 weeks postinjection, Drooling Frequency and Severity Scale scores significantly improved versus placebo (-1.3 ± 1.3) in a dose-related manner (-2.1 ± 1.2, P = 0.0191; -3.3 ± 1.4, P < 0.0001; -3.5 ± 1.1, P < 0.0001, respectively) and unstimulated salivary flow rates significantly decreased in all active groups versus placebo (P ≤ 0.0009). Furthermore, treated subjects appeared to have more sustained improvement in sialorrhea than placebo subjects. We conclude that intraglandular injection of botulinum toxin type B was safe, tolerable, and efficacious in treating sialorrhea in PD patients. Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing.

An open-label, sequential dose-escalation, safety, and tolerability study of rimabotulinumtoxinb in subjects with cervical dystonia.

OBJECTIVES: Evaluate the safety and efficacy of a sequential dose escalation of rimabotulinumtoxinB (BoNT-B) in cervical dystonia (CD) subjects. METHODS: This multicenter, open-label, within-subject, sequential dose-escalation study (BoNT-B dosed at 10,000, 12,500, and 15,000 Units) evaluated subjects over each phase of treatment at preinjection and at periodic intervals postinjection. Adverse events, vital signs, and laboratory results were recorded. Efficacy measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and three visual analog scales (VASs). RESULTS: 119 out of 145 CD subjects received all three doses in sequence. Dry mouth and dysphagia were the most common adverse events, and both decreased in frequency by the final injection, despite the increasing doses of the escalation. TWSTRS-Total and subscale scores demonstrated significant improvements following all doses at the week 2, 4, 8, and 12 assessments, with the exception of disability and pain at week 12 with the lowest dose. All VAS scores demonstrated similar improvements following all doses. The mean number of weeks in each phase of the study was 12.1 weeks (10,000 Units), 12.9 weeks (12,500 Units), and 13.9 weeks (15,000 Units). CONCLUSION: BoNT-B was well tolerated and efficacious at 10,000, 12,500, and 15,000 Units in this within-subject, sequential dose-escalation study in CD subjects.

RimabotulinumtoxinB effects on pain associated with cervical dystonia: results of placebo and comparator-controlled studies.

Response rate (RR) and mean improvement (MI) in the pain subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-PS) from two placebo-controlled studies and one comparator-controlled study were evaluated to examine the effect of rimabotulinumtoxinB (BoNT-B) on cervical dystonia (CD) pain. Subjects receiving either of two doses of BoNT-B in the AN072-301 trial had an RR of 66% and 58% compared with 23% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-302 trial had an RR of 49% compared with 19% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-402 comparator-controlled trial had a significantly higher RR than those treated with BoNT-A (59% vs. 36%; p < .05). Additionally, subjects treated with BoNT-B in these placebo-controlled trials had significantly larger MIs than those treated with placebo (4.3 and 3.7 vs. 0.5 for AN072-301 and 3.6 vs. 0.1 for AN072-302; p < .05). Subjects treated with BoNT-B in the comparator-controlled trial demonstrated a numerically larger MI than those treated with BoNT-A (2.6 vs. 1.8; p = .1651). These results support the consideration of BoNT-B as an effective first-line botulinum toxin treatment for patients with CD who list pain as a primary complaint.