When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.
This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.
The efficacy and safety of abobotulinumtoxinA (Dysport®) for the treatment of upper limb spasticity in children with cerebral palsy (CP) was evaluated in a phase III, multi-center, double blind, prospective, randomized, low-dose controlled, multiple treatment study. A total of 208 botulinum toxin naive or non-naive (66 percent had prior treatment with a botulinum toxin) individuals weighing at least 10 kg, with a baseline Modified Ashworth Score (MAS)* of grade 2 or greater at the primary targeted muscle groups (PTMG), were enrolled in the modified intention to treat population (mITT). Individuals received Dysport® at the following doses: (16 Units/kg up to maximum of 640 U [n=70] ), Dysport® (8 Units/kg up to maximum of 320 U [n=69] ), or Dysport® (2 Units/kg [n=69] ) injected into the upper limb. The elbow flexors and wrist flexors respectively were the PTMG in 57 percent and in 43 percent of individuals.
The primary efficacy endpoint was the mean change from baseline in MAS* in the PTMG at week six. The secondary efficacy endpoint was the mean Physician Global Assessment (PGA)*** score assessed at week six. AbobotulinumtoxinA (Dysport®) demonstrated statistically significant improvements from baseline at week six with doses of 8 Units/kg and 16 Units/kg, as measured by the MAS* in the elbow or wrist flexors.
The most common adverse reactions (more than 10 percent) in pediatric individuals with upper limb spasticity for Dysport were upper respiratory tract infection and pharyngitis.
On June 21, 2019, the FDA approved onabotulinumtoxinA (Botox®) for the treatment of pediatric individuals from two to 17 years of age with upper limb spasticity. The approval for upper limb spasticity was based on a randomized, multi-center, double-blind, placebo-controlled study (NCT01249417 ) that included 234 pediatric individuals, who received the following doses: (78 individuals received Botox® 3 Units/kg, 77 Botox® 6 Units/kg [maximum 200 Units], and 79 placebo) with upper limb spasticity (Modified Ashworth Scale* elbow or wrist score of at least 2) because of cerebral palsy or stroke. Individuals were followed for 12 weeks after injection. Primary endpoints were the average of the change from baseline in modified Ashworth Scale (MAS)* principal muscle group score (elbow or wrist) at week four and week six, and the average of the Clinical Global Impression of Overall Change by Physician (CGI) at week four and week six. The CGI evaluated the response to treatment in terms of how the individual was doing in his/her life using a nine-point scale (minus 4-very marked worsening to plus 4-very marked improvement). Compared to placebo, significant improvements in MAS* change from baseline were observed at all time points for Botox-treated individuals. The CGI scores numerically favored Botox® over placebo, but the difference was not statistically significant.
On July 2016, FDA approved Dysport® for lower limb spasticity in pediatric individuals. The safety and efficacy of Dysport® for the treatment of lower limb spasticity due to cerebral palsy causing dynamic equinus foot deformity in pediatric individuals from two to 17 years of age was evaluated in a double-blind, placebo-controlled, multicenter study. A total of 235 (158 Dysport® and 77 placebo) toxin-naive or non-naive individuals with a Modified Ashworth Score (MAS)* of grade 2 or greater at the ankle plantar flexors were enrolled to receive Dysport® at the following doses: 10 Units/kg/leg (n=79), Dysport® 15 Units/kg/leg (n=79) or placebo (n=77) injected into the gastrocnemius and soleus muscles. Forty-one percent of individuals (n=66) were treated bilaterally and received a total lower limb Dysport® dose of either 20 Units/kg (n=37) or 30 Units/kg (n=29). The primary efficacy endpoint was the mean change from baseline in MAS* in ankle plantar flexor at week four; a co-primary endpoint was the mean Physician’s Global Assessment (PGA)*** score at week four. Study results showed an improvement in Dysport® group versus placebo on muscle tone at both doses at week four post-injection (Primary endpoint – Assessment scale: Modified Ashworth Scale)*.
The Physician’s Global Assessment treatment differences versus placebo were also significant.
The most frequent treatment emergent adverse events were common childhood infections (upper respiratory tract infections).
On October 15, 2010, the FDA approved onabotulinumtoxinA (Botox®) for prophylaxis of headaches in adults with chronic migraine headache (at least 15 days per month with headache lasting at least 4 hours per day). The approval for chronic migraine was based on results of the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) program, which consisted of 2 double-blind, placebo-controlled clinical trials that included 1384 adults from 122 centers in North America and Europe. In both of these studies, individuals receiving onabotulinumtoxinA (Botox®) had a significantly greater decrease in the frequency of headache days from baseline compared with placebo at 24 weeks: 7.8 and 9.2 fewer days for the treated groups vs. 6.4 and 6.9 days for the placebo groups, respectively. Treated individuals also had a total cumulative reduction in headache hours by 107 and 134 hours, respectively, compared with 70 and 95 hours for the placebo groups.
On April 29, 2009, abobotulinumtoxinA (Dysport®) was approved by the FDA for the treatment of cervical dystonia. AbobotulinumtoxinA (Dysport®) was evaluated in two randomized, double blind, placebo controlled, single dose, parallel group studies in treatment-naïve cervical dystonia individuals. 252 individuals were enrolled. The primary assessment of efficacy was based on the total Toronto Western Spasmodic Torticolls Rating Scale (TWSTRS) change from baseline at Week 4 for both studies. The scale evaluates the severity of dystonia, individual perceived disability from dystonia, and pain. The adjusted mean change from baseline in the TWSTRS total score was statistically significantly greater for the abobotulinumtoxinA (Dysport®) group than the placebo group at Weeks 4 in both studies.
On December 8, 2000, FDA approved rimabotulinumtoxinB (Myobloc®) for the treatment of cervical dystonia. The approval for cervical dystonia was based on two phase three, randomized, multi-center, double-blind, placebo-controlled studies. Both studies enrolled only adult individuals who had a history of receiving botulinum toxin type A. Study #301 enrolled individuals who were perceived as having an acceptable response to type A toxin, while Study #302 enrolled only individuals who had secondarily lost responsiveness to type A toxin. Study #301 enrolled 109 individuals, and 77 individuals were enrolled into Study #302. Individual evaluations continued for 16 weeks post injection. The primary efficacy outcome variable for both studies was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score (scale range of possible scores is 0–87) at Week 4. The secondary endpoints were the Patient Global and Physician Global Assessments of change at Week 4. TWSTRS Total Score at Week 4 and Patient Global Assessment among subgroups by gender or age showed consistent treatment-associated effects across these subgroups.
*Modified Ashworth Scale (MAS) score measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Scoring is 0 - No increase in muscle tone to 4 - Affected part(s) rigid in flexion or extension.
**The GAS is a functional 5-point scale used to measure progress towards individual therapy goals.
***The Physician Global Assessment (PGA) is a 5-point or 6-point scoring system used to assess disease severity.
Cosmetic services are those provided to improve an individual's physical appearance, from which no significant improvement in physiologic function can be expected. Emotional and/or psychological improvement alone does not constitute improvement in physiologic function.
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issues by leading professional organizations and government entities.
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Adler CH, Bansberg SF, Krein-Jones K, Hentz JG. Safety and efficacy of botulinum toxin type B (Myobloc) in adductor spasmodic dysphonia. Mov Disord. 2004;19(9):1075-1079.
Allergan, Inc., Irvine, California. OnabotulinumtoxinA (Botox®) Product Information. [Allergan Web site]. Updated 10/2019. Available at: http://www.botox.com/ and https://www.botoxspasticity.com/about-spasticity/causes. Accessed April 08, 2020.
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ClinicalTrials.gov. BOTOX® Treatment in Pediatric Lower Limb Spasticity. Identifier: NCT01603628. First Posted: May 22,2012; Last Update Posted: August 14, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT01603628?term=NCT01603628&draw=2&rank=1. Accessed April 12, 2020.
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Policy: 08.00.15f:Off-label Coverage for Prescription Drugs and/or Biologics
Policy: 11.05.07d:Surgical Correction of Strabismus