LCD L33274: Botulinum Toxins

Clostridium botulinum toxin describes a family of neurotoxins produced by the anaerobic bacteria of the species C botulinum. There are 7 distinct serotypes of botulinum toxin: A, B, C, D, E, F, and G. All botulinum neurotoxin serotypes are understood to produce their clinical effect by blocking the release of the neurotransmitters, principally acetylcholine, from nerve endings. 1 There are 5 distinct serotype A botulinum toxin products, onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), prabotulinumtoxinA-xvfs (Jeuveau), and daxibotulinum toxin A (Daxxify) and 1 serotype B botulinum toxin product, rimabotulinumtoxinB (Myobloc) that have been approved by the FDA. PrabotulinumtoxinA-xvfs (Jeuveau) is indicated for cosmetic use only. 2

Whether a botulinum toxin is produced from the same or different serotype producing strain, they undergo different manufacturing processes which yield differences in the size and weight of the molecules. Because of this, Botox, Dysport, Xeomin, Myobloc, and Daxxify, as well as other botulinum toxin products available internationally, are not interchangeable. They are chemically, pharmacologically, and clinically distinct. 1

For the purposes of this LCD, botulinum toxin injections (BTI) refers to the general use of these products as a whole. Each specific product will be discussed by name. BTI are commonly used to treat a wide variety of conditions in which the main therapeutic effect is to decrease undesired or excessive contraction of striated or smooth muscle. They produce a presynaptic neuromuscular blockade by preventing the release of acetylcholine from the nerve endings. 1 The resulting chemical denervation of muscle produces local paresis or paralysis and allows individual muscles to be weakened selectively.

Covered Indications

NOTE: The 5 botulinum therapies are not interchangeable and are only covered as listed below.

Botulinum toxins (Botox, Dysport, Xeomin, Myobloc, and Daxxify), will be considered reasonable and necessary when administered for treatment of FDA-labeled indications and off-label indications (as applicable) below:

• FDA indications for onabotulinumtoxinA (Botox) as noted on the FDA website: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103000 3

• Off-Label indications for onabotulinumtoxinA (Botox) are considered reasonable and necessary in patients for the following conditions:

• Esophageal achalasia in the following circumstances:

• Medically high-risk patients who cannot undergo other invasive treatments (peroral endoscopic myotomy [POEM], Heller myotomy, pneumatic dilation [PD]) 4-12

• As a bridge for those awaiting more effective treatments such as Heller myotomy, PD, or POEM 10

• During work-up and treatment planning of definitive treatments for achalasia 13,14

• Chronic anal fissure for patients with inadequate response to conservative or pharmacologic treatment 15

• Essential hand tremor for patients with a high amplitude tremor that disrupts activities of daily living and have had inadequate response to oral pharmacotherapy such as propranolol and primidone 16

• Focal hand and limb dystonia 16

• Hemifacial spasm in adults (cranial nerve VII disorder) 16

• Isolated oromandibular dystonia (also known as orofacial dystonia, isolated oromandibular dystonia, oromandibular dystonia, blepharospasm associated with orofacial dystonia, and Meige syndrome) in adults 17

• Laryngeal dystonia (spastic dysphonia) for adductor type (ADSD) 16

• Bothersome simple motor tics in adolescents and adults when the benefits of treatment outweigh the risks 18

• Severely disabling or aggressive vocal tics in older adolescents and adults when the benefits of treatment outweigh the risks 18

• FDA indications for abobotulinumtoxinA (Dysport) as noted on the FDA website: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125274 19

• Off-label indications for abobotulinumtoxinA (Dysport) are considered reasonable and necessary in patients for the following conditions:

• Blepharospasm in adults 16,17

• Hemifacial spasm in adults (cranial nerve VII disorder) 16

• Isolated oromandibular dystonia (also known as orofacial dystonia, isolated oromandibular dystonia, oromandibular dystonia, blepharospasm associated with orofacial dystonia, and Meige syndrome) in adults 17

• FDA indications for incobotulinumtoxinA (Xeomin) as noted on the FDA website: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125360 20

• FDA indications for rimabotulinumtoxinB (Myobloc) as noted on the FDA website: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103846 21

• FDA indications for daxibotulinumtoxinA-lanm (Daxxify) as noted on the FDA website: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761127 . 22

Limitations

• Localization procedures would not be expected and therefore considered not reasonable and necessary for easily targeted muscles. 17,23

• Administration of onabotulinumtoxinA (Botox) for achalasia in the following circumstances is considered not reasonable and necessary:

• Patients with contraindications for Botox or upper endoscopy. 24

• Injection of botulinum toxin in the esophageal body. 6,8-10

• Treatment of isolated lower limb dystonia and isolated exercise-associated lower limb dystonia is considered not reasonable and necessary. 25

• Treatment of abductor spasmodic dysphonia is considered not reasonable and necessary. 26

• Treatment of wrinkles, also called glabellar lines, smoker’s lines, crow’s feet, laugh lines, and aging neck, using botulinum toxins, are considered cosmetic procedures and not covered under Medicare.

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

Off-Label Indications Supported by Evidence-Based Guidelines

Botulinum toxin is used therapeutically to reduce pathologic muscle contraction. Health outcomes of interest are improved function and improved quality of life.

The American Academy of Neurology (AAN) has produced a clinical practice guideline process manual that includes a discussion regarding elements of recommendations and levels of evidence (see tables below). 27

Level (Quality) of Evidence