Results from a pooled analysis extend and support the safety and the tolerability of the use of incobotulinumtoxinA for the treatment of adults with neurological disorders.
Study findings presented by Cynthia Comella, MD, and colleagues at the 2022 International Parkinson and Movement Disorders Society Congress, held September 15-18, in Madrid, Spain, on the treatment of incobotulinumtoxinA for adults established by individual clinical studies suggest that the treatment is safe and tolerable in adults with neurological disorders.1
Comella et al wrote that they, “investigated the pooled incidence of treatment-emergent adverse events and immunogenicity by indication in sponsored [incobotulinumtoxinA].” Comella, a professor in the Department of Neurological Sciences at Rush University Medical Center, and colleagues noted that although the safety and efficacy of incobotulinumtoxinA in adult neurological disorders has been investigated in previous clinical trials, several of them have yet to be published. Therefore, the group concluded, this study’s comprehensive assessment on incobotulinumtoxinA, with the combined data available, provided additional insight into its safety for adults with neurological disorders.
From the study's results, the incidences of overall treatment-emergent adverse events (TEAEs) were similar between incobotulinumtoxinA and Merz-sponsored placebo in all indications, although between-indication differences were observed.1 Most TEAEs observed were mild to moderate in intensity, and only 1 participant experienced a TR-serious adverse event. Other findings included that few TEAEs led to discontinuation of incobotulinumtoxinA; there were no fatal TEAEs in subjects receiving incobotulinumtoxinA.
Overall, the repeated cycles did not increase the incidences of any TEAE category as the most frequent TEAEs and TR-TEAEs were indication-dependent.1 The TEAEs included the outcomes of nasopharyngitis, diarrhea and headache while the TR-TEAEs included dysphagia for indications affecting the head or neck. Comella et al noted that, “few subjects developed neutralizing antibody; the vast majority of those positive at the end of the study were also positive at baseline.” TR-TEAEs affected 1% of patients and were found to be uncommon in patients with spasticity. Across all indications, TR-AESIs, a special interest TEAEs indicating possible toxin spread, were most commonly muscular weakness as well as dry mouth.
“In patients who were reported as treatment-naïve at baseline, there was no observable pattern of HDA positivity at study end, with 50% of these patients being HDA positive at screening; the vast majority of positive HDA values were only marginally above the threshold of positivity, and the evolution of HDA values in individual patients did not correlate with the investigator's judgment of efficacy,” Comella et al noted.
The method of the study had the TEAEs identified in an integrated clinical database of Merz-sponsored placebo-controlled studies in adults with cervical dystonia, blepharospasm, upper limb (UL) and lower limb spasticity, sialorrhea and essential tremor of the UL.1 Overall incidences of TEAEs and the categories of serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection cycle and for incobotulinumtoxinAafter multiple cycles.As for the most frequent TEAEs, TR-TEAEs and TR-AESIs were summarized after a single cycle of incobotulinumtoxinA while the neutralizing antibody (NAb) test was performed in most of the studies.
A previous study had repeated injections of incobotulinumtoxinA for the treatment of post-stroke upper-limb spasticity which led to significant improvements in muscle tone and investigator's global impression of change.2 Another study mentioned that incobotulinumtoxinA reduced (pathologically) increased muscle tone, improved functionality and was well tolerated in Japanese subjects with post stroke upper-limb spasticity.3 Past studies with the use of incobotulinumtoxinA for treatment of neurological disorders such as for post-stroke for adults have concluded the safety to be favorable.
In the study with the pooled analysis, incobotulinumtoxinA had a supportive safety profile across all neurological disorders that were investigated and showed no unexpected safety findings.1 Future studies should continue to research the effectiveness of incobotulinumtoxinA and its association with a low rate of NAb formation as patients reported positive test results at screening and at their last study visit.