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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Treatment
Policy Number:059
Effective Date: 09/11/2020
Original Policy Date:01/01/1993
Last Review Date:09/08/2020
Date Published to Web: 09/04/2019
Subject:
Botulinum Toxin

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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Botulinum is a family of toxins produced by the anaerobic organism Clostridia botulinum. There are seven distinct serotypes designated as type A, B, C-1, D, E, F, and G. Botulinum toxin is a powerful neuroparalytic agent that paralyzes muscles. When minute quantities are injected into spastic muscles, local denervation and muscle weakness occur thereby causing remission of symptoms. In the United States, four preparations of botulinum toxins produced by 2 different strains of bacteria are available: type A (Botox, Dysport, and Xeomin) and type B (Myobloc). When administered intramuscularly, all botulinum toxins reduce muscle tone by interfering with the release of acetylcholine from nerve endings.

OnabotulinumtoxinA, formerly known as botulinum toxin type A, (marketed as Botox by Allergan) was the first serotype to be approved by the US FDA for use in specific disorders of the eye, facial, and neck muscles in 1989. In April 2002, the US FDA granted approval to onabotulinumtoxinA, formerly known as botulinum toxin type A (marketed as Botox Cosmetic by Allergan) to temporarily improve the appearance of moderate to severe frown lines between the eyebrows (glabellar lines). In July 2004, Botox received FDA approval for the treatment of severe primary axillary hyperhidrosis. In August 2011, Botox received FDA approval for treatment of urinary incontinence in people with spinal cord injury and multiple sclerosis who have overactivity of the bladder. OnabotulinumtoxinA is also FDA-approved for several disorders, including cervical dystonia, blepharospasm, strabismus, and most recently upper limb spasticity. In January 2013, Botox received FDA approval for treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have inadequate response to or are intolerant to anticholinergic medication.

In January 2016, Botox received FDA approval for treatment of lower limb spasticity. The approval was based on a randomized (1:1), multi-center, double-blind, placebo-controlled trial of 468 patients who were at least 3 months post-stroke. A total dose of 300 Units of Botox or placebo were injected intramuscularly and divided between the gastrocnemius, soleus, and tibialis posterior with optional injection of up to an additional 100 Units (for 400 Units total dose) into the flexor halluces longus, flexor digitorum longus, flexor digitorum brevis, extensor halluces, and rectus femoris. Patients were then followed for 12 weeks. The co-primary endpoints were the average of the change from baseline in modified Ashworth Scale (MAS) ankle score and the average of the Physician Global Assessment of Response (CGI) at week 4 and week 6. MAS score is a 6 point clinical rating tool to measure spasticity and assess drug therapy (0= no increase in muscle tone, 4= affected muscle is in a rigid flexion or extension position). The CGI evaluated the response to treatment in terms of how the patient was doing in his/her life using a 9-point scale (from -4=very marked worsening to +4=very marked improvement). Statistically significant differences in Botox over placebo were seen in the change in MAS and CGI scores at weeks 4 and 6 (p<0.05). The most frequently reported adverse reactions following Botox injection were arthralgia (3%), back pain, (3%), myalgia (2%), upper respiratory tract infection (2%), and injection site pain (2%). On June 20, 2019 the FDA extended use for the treatment of upper limb spasticity to include children aged 2-17 years old. The approval was based on a randomized, multi-center, double-blind, placebo-controlled trial. The study included 234 pediatric patients with upper limb spasticity due to cerebral palsy or stroke. A total dose of 3 Units/kg of Botox, 6 Units/kg of Botox or placebo was injected intramuscularly and divided between the wrist or elbow and finger muscles. The co-primary endpoints were the average change from baseline in MAS principle muscle group score (elbow or wrist) at Week 4 and Week 6, and the average CGI at Week 4 and 6. Significant improvements in MAS change from baseline were observed at both Week 4 and Week 6 for Botox-treated patients (p<0.05). Although CGI scores numerically favored Botox, the difference was not statistically significant. Both doses showed similar effects in MAS and CGI score changes. The most frequently reports adverse reactions were upper respiratory tract infection (17% in 6 Units/kg, 10% in 3 Units/kg, 9% in placebo), injection site pain (4% in 6 Units/kg, 3% in 3 Units/kg, 1% in placebo) and seizure (5% in 6 Units/kg, 1% in 3 Units/kg and 0% in placebo).

On July 9, 2020, the FDA approved the expanded use of BOTOX® (onabotulinumtoxinA) for the treatment of spasticity in pediatric patients 2 years of age and older, including those with lower limb spasticity caused by cerebral palsy.

RimabotulinumtoxinB, formerly known as botulinum toxin type B, (marketed as Myobloc by Solstice Neurosciences) was approved by the US FDA on December 8, 2000 for use in cervical dystonia. On August 20, 2019 Myobloc received FDA expanded approval for the treatment of chronic sialorrhea in adult patients. The approval was based on two phase-3 multicenter, double-blind, placebo-controlled, single-treatment studies. In the first study, 187 adult patients with chronic, troublesome sialorrhea for at least 3 months were randomized to receive Myobloc 2,500 Units, Myobloc 3,500 units, or placebo. Most patients had chronic sialorrhea associated with Parkinson’s, ALS, stroke or other causes. The co-primary efficacy endpoints for Study 1 were the change from baseline in Unstimulated Salivary Flow Rate (USFR) and the Clinical Global Impression of Change (CGI-C) assessed 4 weeks after treatment in the double-blind part of the study. The change from baseline in USFR at Week 4 was significantly greater for patients treated with Mybloc than in patients on placebo (p<0.0001). Similarly, CGI-C scores at Week 4 were significantly greater in patients treated with Myobloc than in patients on placebo (p<0.0001). The second study was conducted in 54 patients diagnosed with Parkinson’s and troublesome chronic sialorrhea. Patients were randomized to receive a single treatment of Myobloc 1,500 Units, Myobloc 2,500 Units or Myobloc 3,500 Units. Each group also included 5 patients who received placebo. The change from baseline in the USFR and CGI-C was assessed 4 weeks after treatment. There was a significant reduction in the USFR and CGI-C for all three dosage groups of Myobloc, compared to patients with placebo (p<0.0001 for both co-primary endpoints). Changes were similar across all three Myobloc dosage groups. The most common adverse reactions in both studies were dry mouth, dental caries and dysphagia.

AbobotulinumtoxinA (marketed as Dysport by Ipsen) was approved by the US FDA on April 30, 2009 for use in cervical dystonia. AbobotulinumtoxinA is also approved for the temporary improvement in the appearance of moderate to severe glabellar lines in adults younger than 65 years of age (marketed as Dysport by Medicis). On July 16th, 2015 AbobotulinumtoxinA was approved for the treatment of upper limb spasticity in adults. On July 29th, 2016, AbobotulinumtoxinA was approved for the treatment of lower limb spasticity in pediatrics.

On June 16th, 2017 Abobutinumtoxin A was approved for the treatment of lower limb spasticity in adults. Approval was based on a phase III randomized placebo controlled study assessing the safety and efficacy of Abobutinumtoxin A in treating lower limb spasticity in the adult population. Patients were randomized into receiving placebo, 1000 units, or 1500 units of Abobutinumtoxin A every 12-16 weeks. Injections were administered in lower limb muscles including tibialis posterior, flexor digitorum longus, and/or flexor hallucis longus. Primary endpoint measured changes in the patient MAS score at week 4 and results showed a decrease from baseline with Abobutinumtoxin A administration (placebo: -0.5, 1000 units Dysport: -0.6, 1500 units Dysport: -0.8; p<0.05). The most common adverse reactions included falls (9%, 6%, 3%), muscular weakness (2%, 7%, 3%), and pain in extremities (6%, 6%, 2%).

On September 25, 2019, the United States Food and Drug Administration (FDA) expanded the use of Dysport to include the treatment of upper limb spasticity in pediatric patients two years of age and older, excluding spasticity caused by cerebral palsy. The efficacy and safety of Dysport for the treatment of upper limb spasticity in adults was evaluated in a randomized, multicenter, double-blind, placebo-controlled study that included 238 patients (159 Dysport and 79 placebo) with upper limb spasticity (Modified Ashworth Scale (MAS) score ≥2 in the primary targeted muscle group for toxin-naive patients or MAS score ≥3 in the primary targeted muscle group for toxin non-naive patients at least 4 months after the last botulinum toxin injection, of any serotype) who were at least 6 months post-stroke or post-traumatic brain injury. In the clinical trial, doses of 8 Units/kg or 16 Units/kg were divided among selected muscles of the target upper limb at a given treatment session.

IncobotulinumtoxinA (marketed as Xeomin by Meriz) was approved by the US FDA on July 30, 2010 for use in adult patients with cervical dystonia who have previously been treated with botulinum toxin or who are treatment-naïve. IncobotulinumtoxinA is also approved for the treatment of blepharospasm in adult patient previously treated with onabotulinumtoxinA. In May 2019, IncobotulinumtoxinA (Xeomin) was approved as first line treatment of blepharospasm in adult patients. The US FDA on July 21, 2011 also approved incobotulinumA for temporary improvement in the appearance of moderate to severe glabellar (frown) lines between the eyebrows in adult patients. In August 2020, the FDA approved the use of Xeomin (incobotulinumtoxinA) for the treatment of upper limb spasticity in adults and in pediatric patients 2 to 17 years, excluding spasticity caused by cerebral palsy.


[INFORMATIONAL NOTE: All the botulinum toxin products (Botox, Myobloc, Dysport, and Xeomin) carry the following Black Box Warning:

Distant Spread of Toxin Effect: Postmarketing reports indicate that the effects of all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

The requirements of the Horizon BCBSNJ Botulinum Toxin Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

[INFORMATIONAL NOTE: The P&T Committee at Horizon Blue Cross Blue Shield of New Jersey subjects each prescription drug being considered for formulary placement to a rigorous clinical analysis. Based on the scope of indications, clinical efficacy, and safety profile, the P&T Committee recommends the placement of onabotulinumtoxinA (Botox) as preferred botulinum toxin agent.

I. Botulinum toxin treatments must be ordered and monitored by the treating physician who is experienced in the use of such neurolytic agents.

II. Member must not have concomitant treatment with any other botulinum toxin agents.

III. Botulinum toxin injections are considered medically necessary for any of the following FDA-approved indications

    1. Treatment of blepharospasm (Botox, Xeomin only)
        • In members 12 years of age or older (Botox)
        • In members 18 years of age or older (Xeomin)
    2. Treatment of strabismus in members greater than 12 years of age (Botox only)
    3. Treatment of cervical dystonia (spasmodic torticollis) when all of the following criteria are met:
      a. Member has sustained head tilt OR abnormal posturing with limited range of motion in the neck; AND
      b. Member has a history of involuntary contraction of one or more muscles in the neck; AND
      c. Member is at least:
        • 16 years of age (Botox)
        • 18 years of age (Dysport, Myobloc, and Xeomin)
    4. Treatment of severe primary axillary hyperhidrosis in adult members 18 years of age or older when all of the following criteria are met (Botox only):
      a. Member has failed topical agents that contain aluminum (e.g., Drysol, Xerac and/or Hypercare 20%); AND
      b. Member has medical complications OR significant impact to activities of daily living due to this condition
    5. Treatment of spasticity
      • of the upper limbs in adult members (at least 18 years of age) (Botox, Dysport, and Xeomin)
      • of the upper limbs in pediatric members (2-17 years of age) (Botox, Dysport)
      • of the upper limbs in pediatric members (2-17 years of age), excluding spasticity caused by cerebral palsy (Xeomin only)
      • of the lower limbs in adult members (at least 18 years of age) (Botox, Dysport)
      • of the lower limbs in pediatric members (2-17 years of age) (Botox, Dysport)
    6. Incontinence due to detrusor overactivity associated with a neurologic condition [e.g., spinal cord injury, multiple sclerosis] that is inadequately controlled with anticholinergic therapy in adult members 18 years of age or older (Botox only)
    7. Prophylaxis of migraine headaches when all of the following criteria are met (Botox only):
      a. Member has an established diagnosis of
        • Chronic migraine headaches (lasting >15 days per month) for >3 months; AND
        • Headaches with diagnostic-migraine features for 8 days per month for > 3 months defined below:
          • For migraine without aura (need to meet both characteristics noted below)
              • At least two of the following four characteristics:
                1. unilateral location
                2. pulsating quality
                3. moderate or severe pain intensity
                4. aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)
              • At least one of the following during headache:
                1. nausea and/or vomiting
                2. photophobia and phonophobia
          • For migraine with aura (need to meet both characteristics noted below)
              • One or more of the following fully reversible aura symptoms
                1. visual
                2. Sensory
                3. speech and/or language
                4. motor
                5. brainstem
                6. Retinal and
              • At least three of the following six characteristics:
                1. at least one aura symptom spreads gradually over 5 minutes
                2. two or more aura symptoms occur in succession
                3. each individual aura symptom lasts 5–60 minutes
                4. at least one aura symptom is unilateral
                5. at least one aura symptom is positive
                6. the aura is accompanied, or followed within 60 minutes, by headache AND
      b. Member has failed trials of one preventive/prophylactic pharmacologic therapies for migraine headaches (e.g., beta-blockers, calcium channel blockers, anticonvulsants, antidepressants, candesartan, etc.). AND
      c. Member is 18 years of age or older; AND
      d. Suspected migraine is relieved by a triptan or ergot derivative; AND
      e. Botox will not be concomitantly used with a Calcitonin Gene-Related Peptide (CGRP) receptor antagonist that is used for preventative treatment of migraines (eg, Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Vypeti (eptinezumab-jjmr))
    8. Treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency, in adults (18 years of age or older) who have inadequate response to or are intolerant to anticholinergic medication (Botox only)
    9. Treatment of chronic sialorrhea due to:
      • Parkinson’s disease, atypical parkinsonism, stroke or traumatic brain injury, in adults (18 years of age or older) (Xeomin only)
        a. The member has tried and failed one conventional agent prerequisite (e.g glycopyrrolate) OR
        b. The member has a documented intolerance, FDA labeled contraindication, or hypersensitivity to all conventional agent prerequisites
      • Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stroke, or secondary to any other cause for at least a 3-month period, in adults (18 years of age or older) (Myobloc only)
      a. The member has tried and failed one conventional agent prerequisite(e.g glycopyrrolate) OR
        b. The member has a documented intolerance, FDA labeled contraindication, or hypersensitivity to all conventional agent prerequisites
    [INFORMATIONAL NOTE:
    • According to the US Headache Consortium's pharmacological management guidelines for the prevention of migraine, each pharmacologic therapy must be given an adequate trial. A clinical benefit may take as long as two to three months to manifest itself. Contraindications to a pharmacologic therapy (e.g., beta-blockers are contraindicated in patients with asthma) or intolerable side effects are considered treatment failures.]
    • Although rimabotulinumtoxinB (Myobloc) is FDA-approved only for the treatment of cervical dystonia, for purposes of this policy, it may be considered medically necessary for the same FDA-approved indications as onabotulinumtoxinA (Botox). In recent years, the published medical literature has supported the use of rimabotulinumtoxinB (Myobloc) for the general applications for which onabotulinumtoxinA (Botox) is accepted. While recognizing that these agents are not identical, and that the therapeutic and adverse event profiles may differ slightly, practitioners may make the decision as to which agent to use.
    • According the FDA approved package inserts of all four botulinum toxin preparations, the potency units are specific to the preparation and assay methods utilized and as a result, the preparations are not interchangeable and thus cannot be converted.
    • AbobotulinumtoxinA (Dysport) is also known as botulinum type A toxin-haemagglutinin complex outside the US and is the same serotype as Botox. IncobotulinumtoxinA (Xeomin) is also known as botulinum toxin type A and is produced from fermentation of Hall strain Clostridium botulinum serotype A.
    • Dysport, Xeomin, and Botox all have the same mechanism of action by targeting the SNAP-25 protein to inhibit acetylcholine. Dysport has differences in potency due to its LD 50 mouse assay preparation as well as its formulation, which results in a different protein load compared to Botox
    • Botulinum toxins treatments carry the following contraindications:
      • Hypersensitivity to any botulinum toxin preparation or any component of the formulation (Botox, Myobloc, Dysport, and Xeomin)
      • Infection at the proposed injection site (Botox, Myobloc, Dysport, and Xeomin)
      • Urinary tract infection or urinary retention if intradetrusor injection (Botox)
      • Allergy to cow’s milk protein (Dysport)]

IV. Botulinum toxin treatments are also considered medically necessary for the following off-label uses (Botox only):
    1. intrasphincteric injection for achalasia
    2. oromandibular dystonia (orofacial dyskinesia or Meige syndrome, jaw-closing dystonia)
    3. spasmodic dysphonia or laryngeal dystonia (adductor type)
    4. dynamic limb contracture in ambulatory children (by improving gait, and by improving ankle dorsiflexion to permit strengthening and growth of muscles and to delay or prevent surgery with its associated health risks.)
    5. severe focal hyperhidrosis, other than severe axillary hyperhidrosis, when member meets the following criteria:
      • Failed with topical agents; AND
      • Failed with iontophoresis; AND
      • Has functional impairment (i.e. inability perform critical activities of daily living due to condition)
    (NOTE: For severe axillary hyperhydrosis, please refer to policy statement #II.)
    6. chronic anal fissure that has failed conventional therapy
    7. treatment-refractory sialorrhea in advanced Parkinson’s disease and amyotrophic lateral sclerosis
    8. hemifacial spasm

[INFORMATIONAL NOTE: In August of 2015 the following was added to the package insert for Botox:
Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received BOTOX injections for unapproved uses. In these cases, the adverse reactions were not necessarily related to distant spread of toxin, but may have resulted from the administration of BOTOX to the site of injection and/or adjacent structures. In several of the cases, patients had pre-existing dysphagia or other significant disabilities. There is insufficient information to identify factors associated with an increased risk for adverse reactions associated with the unapproved uses of BOTOX. The safety and effectiveness of BOTOX for unapproved uses have not been established.]

V. Botulinum toxin treatments are also considered medically necessary for the following off-label uses (Dysport Only)
    1. Hemifacial spasm
    2. Blepharospasm in members 18 year of age or older
    3. Severe primary axillary hyperhidrosis
VI. When medical necessity criteria are met, botulinum toxin will be approved initially every 12 months (5 doses) administered at approximately 12 week intervals based on FDA-approved labeling:
    1. Blepharospasm (Botox, Xeomin):
        a. Botox: initial recommended dose is 1.25 Units-2.5 Units injected into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid. The cumulative dose of botulinum toxin treatment for blepharospasm in a 30-day period should not exceed 200 Units.
        b. Xeomin: In treatment-naïve members, the recommended initial total dose of Xeomin is 50 Units (25 Units per eye). In members previously treated with a botulinum toxin A, their past dose, response to treatment, duration of effect, and adverse event history should be taken into consideration when determining the Xeomin dose. The total dose of Xeomin should not exceed 100 Units per treatment session (50 Units per eye).
    2. Strabismus (Botox):
        a. For vertical muscles, and for horizontal strabismus of less than 20 prism diopters: 1.25 Units-2.5 Units in any one muscle.
        b. For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5 Units-5 Units in any one muscle
        c. For persistent VI nerve palsy of one month or longer duration: 1.25 Units-2.5 Units in the medial rectus muscle.
        d. The maximum recommended dose as a single injection for any one muscle is 25 Units.
    3. Cervical dystonia (Botox, Myobloc, Dysport, Xeomin):
        a. Botox: Dosing in initial and sequential treatment sessions should be tailored to the individual member based on the member's head and neck position, localization of pain, muscle hypertrophy, member response, and adverse event history
        a. Myobloc: Recommended initial dose for members with a prior history of tolerating botulinum toxin injections is 2500 to 5000 U divided among affected muscles
        b. Dysport: Initial dose is 500 Units given intramuscularly as a divided dose among the affected muscles
        c. Xeomin: The recommended initial total dose is 120 Units per treatment session
      [INFORMATIONAL NOTE: Limiting the total Botox dose injected into the sternocleidomastoid muscle to 100 Units or less may decrease the occurrence of dysphagia]

    4. Primary Axillary Hyperhidrosis (Botox): recommended dose is 50 Units per axilla
    5. Upper Limb Spasticity (Botox, Dysport, Xeomin)
    a. Botox: For adult members, select dose based on muscles affected, severity of muscle activity, prior response to treatment, and adverse event history; electromyographic guidance recommended. For pediatric members, the recommended dose is 3 units/kg to 6 units/kg divided among the affected muscles with a total dose of Botox administered per treatment session in the upper limb to not exceed 6 units/kg or 200 units, whichever is lower.
    b. Dysport: For adult members, select dose based on muscles affected, severity of muscle spasticity, prior response and adverse reaction history following treatment with botulinum toxins. For pediatric members 2 years of age or older with a weight of at least 10 kg, doses of 8 units/kg or 16 units/kg were divided among selected muscles of the target upper limb at a given treatment session.
    c. Xeomin: For adult members, the recommended total dose is up to 400 Units no sooner than every 12 weeks. For pediatric members, excluding spasticity caused by cerebral palsy, the recommended total dose of 8 units/kg (maximum 200 units) per single upper limb or 16 units/kg (maximum of 400 units) in both upper limbs
    6. Lower Limb Spasticity (Botox, Dysport)
    a. Botox: For adults, rRecommended total dose 300 Units to 400 Units divided across ankle and toe muscles. For pediatrics, the recommended dose is 4 units/kg to 8 units/kg divided among the affected muscles. The total dose of Botox administered per treatment session in the lower limb should not exceed 8 units/kg or 300 units, whichever is lower.
    b. Dysport: For treatment of pediatric lower limb spasticity, the recommended total dose per treatment session is 10 to 15 units/kg for unilateral lower limb injections or 20 to 30 units/kg for bilateral lower limb injections.
    For treatment of adult lower limb spasticity, the recommended total dose per treatment is 1000-1500 units not to exceed 1500 units total.
      [INFORMATIONAL NOTE: In clinical trials, doses ranging from 75 Units to 400 Units were divided among selected muscles at a given treatment session for Botox for treatment of upper limb spasticity. The FDA recommended doses for Dysport range from 100 to 400 units depending on the muscle. Botox for treatment of lower limb spasticity has a FDA approved recommended dose of 300 Units to 400 Units divided among 5 muscles (gastrocnemius, soleus, tibialis posterior, flexor halluces longus and flexor digitorum longus. According to the package insert, the recommended total dose for Xeomin is up to 400 units at a frequency of no sooner than every 12 weeks for treatment of upper limb spasticity. According to the package insert, the recommended total dose of Dysport per treatment session for pediatric lower limb spasticity must not exceed 15 units/kg for unilateral lower limb injections, 30 units/kg for bilateral injections, or 1000 units, whichever is lower. When possible, the dose should be distributed across more than 1 injection site in any single muscle; re-treatment should not occur in intervals of less than 12 weeks]

    7. Detrusor overactivity (Botox): recommended dose is 200 Units.
    8. Chronic migraine (Botox): recommended dose is 155 Units per injection site administered intramuscularly
    [INFORMATIONAL NOTE: Injections should be divided across 7 specific head/neck muscle areas as indicated in the prescribing information]

    9 Overactive bladder (detrusor) (Botox): recommended dose is 100 Units
    [INFORMATIONAL NOTE: As per the FDA approved package insert, adult patients treated with Botox for one or more indications, the maximum cumulative dose should not exceed 400 Units in a 3 month interval.]

    10. Chronic Sialorrhea
    a. Xeomin: recommended dose is 100 units (30 units per parotid gland and 20 units per submandibular gland), no sooner than every 16 weeks.
    b. Myobloc: recommended dose is 1,500 Units to 3,500 Units, divided among the parotid and submandibular glands, no more frequent than every 12 weeks.

VII. Continued treatment will be considered medically necessary for 12 months (5 doses) administered at 12 week intervals if:
        • member continues to meet initial review criteria; AND
        • member had disease response; AND
          • Specifically for prophylaxis of migraine headaches:
            • Significant decrease in number and frequency of headaches by at least 7 days per month compared to pretreatment level, or migraine headache duration reduced at least 100 hours per month compared pretreatment level; AND
            • Improvement in function
        • Absence of unacceptable toxicity from the drug (e.g.: botulinum toxin effects).
    • The response to botulinum toxin injections must be documented in the member's medical record after each treatment session. The medical record will be required and must be provided upon request to determine the continued medical necessity of treatment after the first two treatments.
    • If botulinum toxin injections is requested more frequently then every 12 weeks, the rationale must be provided by the requesting physician as to the medical necessity of more frequent injections.

VIII. The use of botulinum toxin treatments is considered investigational in other conditions including, but not limited to, the following: (e.g., anal spasm, irritable colon, biliary dyskinesia, fibromyalgia, focal myofascial pain disorders, chronic back pain, chronic neck pain, interstitial cystitis, detrusor sphincteric dyssynergia, benign prostatic hypertrophy, gastroparesis, piriformis muscle syndrome, tinnitus, chronic tension-type headaches, diabetic neuropathic pain, Raynaud’s phenomenon, chronic pelvic pain), ureteral stent pain reduction, keloids, nocturnal bruxism, idiopathic rhinitis, restless leg syndrome, plantar fascitis, focal cancer pain after surgery or radiation, resting tremor in Parkinson’s disease, scrotal pain or cosmetic (e.g., reduction of glabellar frown lines, elimination of hyperkinetic facial lines or wrinkles).

    [INFORMATIONAL NOTE: The use of botulinum toxin in chronic tension-type headaches is considered investigational as a result of the 2008 recommendation from the American Academy of Neurology. The Academy made the following recommendation: botulinum toxin injections should not be considered in patients with chronic tension-type headache.]
IX. Although EMG (electromyography) guidance is generally not necessary, there may be members who require it (e.g., after initial treatment failure) in order to determine the proper injection site(s).


Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Botulinum Toxin. LCD 35081 states that EMG (CPT codes 95873 and 95874) may be used to optimize the anatomic location of botulinum toxin injection. It is expected there will be one study performed per anatomic location of injection, if needed.
For additional information and eligibility, refer to Local Coverage Determination (LCD): Nerve Conduction Studies and Electromyography (L35081). Available at https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35081&ver=59&name=314*1&UpdatePeriod=749&bc=AAAAEAAAAAAAAA%3d%3d&.

Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy for all codes except 95873 and 95874.
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Botulinum Toxin
Botox
Botox Cosmetic
Myobloc
Toxin, Botulinum
Dysport
Abobotulinum Toxin
Toxin, Abobotulinum
Onabotulinum Toxin
Toxin, Onabotulinum
Rimabotulinum Toxin
Toxin, Rimabotulinum
AbobotulinumtoxinA
OnabotulinumtoxinA
RimabotulinumtoxinB
IncobotulinumtoxinA (Xeomin)
Xeomin (IncobotulinumtoxinA)

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94. Lew MF. Botulinum toxin type B. An effective treatment for alleviating pain associated with cervical dystonia. Journal of Back and Musculoskeletal Rehabilitation. 2002;16:3-9.

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96. Berman B, Seeberger L, Kumar R. Long-term safety, efficacy, dosing and development of resistance with botulinum toxin type B in cervical dystonia. Mov Disord 2005;20(2):233-7.

97. Brashear A, McAfee AL et al. Treatment with botulinum toxin type B for upper-limb spasciticity. Arch Phys Med Rehabil 2003;84(1):103-7.

98. Oechsner M. Treatment of hip adductor spasticity with botulinum toxin type B. Nervenrzt 2002;73(12):1179-82.

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110. Hecht MJ, Birklein F, Winterholler M. Successful treatment of axillary hyperhidrosis with very low doses of botulinum toxin B: A pilot study. Arch Dermatol Res 2004 Feb;295(8-):318-9.

111. Fishman LM, Konnoth C, Rozner B. Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: A dose finding study. Am J Med Rehabil 2003;83:42-50.

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144. Delgado MR, Hirtz D, Aisen M, et al. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2010 Jan 26;74(4):336-43.

145. Gupta M, Patel T, Xavier K, et al. Prospective randomized evaluation of periureteral botulinum toxin type A injection for ureteral stent pain reduction. J Urol. 2010 Feb;183(2):598-602.

146. Lee SJ, McCall WD Jr, Kim YK, et al. Effect of botulinum toxin injection on nocturnal bruxism: a randomized controlled trial. Am J Phys Med Rehabil. 2010 Jan;89(1):16-23.

147. Rohrbach S, Junghans K, Köhler S, et al. Minimally invasive application of botulinum toxin A in patients with idiopathic rhinitis. Head Face Med. 2009 Oct 16;5:18.

148. Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: The care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73(15):1227-33.

149. Shuhendler AJ, Lee S, Siu M, et al. Efficacy of botulinum toxin type A for the prophylaxis of episodic migraine headaches: a meta-analysis of randomized, double-blind, placebo-controlled trials. Pharmacotherapy. 2009 Jul;29(7):784-91.

150. Xeomin [prescribing information]. Reensboro, NC: Merz Pharmaceuticals; August 2020.

151. Botox [prescribing information]. Madison, NJ: Allergan, Inc; July 2020. Available from: http://www.allergan.com/assets/pdf/botox_pi.pdf

152. Myobloc [prescribing information]. Solstice Neurosciences, Inc. August 2019.

153. FDA Approves Botox to treat urinary incontinence in people with neurologic conditions such as spinal cord injury and multiple sclerosis who have overactivity of the bladder. August 25, 2011. Available from: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm269509.htm

154. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. OnabotulinumtoxinA. Available at: http://www.micromedexsolutions.com. Accessed November 5, 2019.

155. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. RimabotulinumtoxinB. Available at: http://www.micromedexsolutions.com. Accessed March 09, 2015.

156. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. AbobotulinumtoxinA. Available at: http://www.micromedexsolutions.com. Accessed March 09, 2015.

157. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. IncobotulinumtoxinA. Available at: http://www.micromedexsolutions.com. Accessed March 09, 2015.

158. Clinical Pharmacology [database online]. OnabotulinumtoxinA. Gold Standard; 2009. Updated December 16, 2014. Accessed March 09, 2015.

159. Clinical Pharmacology [database online]. RimabotulinumtoxinB Gold Standard; 2009. Updated February 17, 2010. Accessed March 09, 2015.

160. Clinical Pharmacology [database online]. AbobotulinumtoxinA Gold Standard; 2009. Updated January 26, 2015. Accessed November 5, 2019.

161. Clinical Pharmacology [database online]. IncobotulinumtoxinA Gold Standard; 2009. Updated July 25, 2011. Accessed March 09, 2015.

162. Botulinum Toxin. In: McEvoy GK, editor. AHFS: Drug Information (2015). Bethesda, MD: American Society of Health-System Pharmacists; 2015. Updated July 16, 2012. Accessed March 09, 2015. http://online.statref.com/Document.aspx?fxId=1&docId=1591

163. Wolosker N, de Campos JR, Kauffman P, Puech-Leão P, A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis. J Vasc Surg. 2012Jun;55(6):1696-700.

164. U.S. Food and Drug Administration (FDA). MedWatch – the FDA Safety Information and Adverse Event Reporting Program – BOTOX Safety Information. Updated August 2015. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm460726.htm

165. Allergan. BOTOX Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited Feb 5, 2016]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01575054 NLM Identifier: NCT01575054

166. Delgado MR, Tilton A, Russman B, et al. AbobotulinumtoxinA for equinus foot deformity in cerebral palsy: a randomized controlled trial. Pediatrics. 2016 Feb;137(2):e20152830. doi: 10.1542/peds.2015-2830. Epub 2016 Jan 26.

167. Wolosker N, de Campos JR, Kauffman P, Puech-Leão P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis. J Vasc Surg. 2012 Jun;55(6):1696-700.

168. Schollhammer M, Brenaut E, Menard-Andivot N, Pillette-Delarue M, Zagnoli A, Chassain-Le Lay M, Sassolas B, Jouan N, Le Ru Y, Abasq-Thomas C, Greco M, Penven K, Roguedas-Contios AM, Dupré-Goetghebeur D, Gouedard C, Misery L, Le Gal G. Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial. Br J Dermatol. 2015;173(5):1163.

169. Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006 Jan 1;73(1):72-8.

170. Perry WB, Dykes SL, Buie WD, Rafferty JF, Standards Practice Task Force of the American Society of Colon and Rectal Surgeons. Practice parameters for the management of anal fissures (3rd revision). Dis Colon Rectum. 2010 Aug;53(8):1110-5.

171. Solish N, Bertucci V, Dansereau A, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg. 2007 Aug;33(8):908-23.

172. Headache Classification Committee Of The International Headache Society (IHS) The International Classification Of Headache Disorders, 3Rd Edition". Vol 38, no. 1, 2018, pp. 1-211. SAGE Publications,

173. Clinicaltrials.gov IncobotulinumtoxinA available at: https://clinicaltrials.gov/ct2/results?cond=&term=xeomin&cntry=&state=&city=&dist=

173. Clinicaltrials.gov Dysport. available at: https://clinicaltrials.gov/ct2/results?cond=&term=dysport&cntry=&state=&city=&dist=

174. Clinicaltrials.gov Botox. available at: https://clinicaltrials.gov/ct2/results?cond=&term=botox&cntry=&state=&city=&dist=

175. Clinicaltrials.gov Myobloc. available at: https://clinicaltrials.gov/ct2/results?cond=&term=myobloc&cntry=&state=&city=&dist=

176. Aimovig [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2019.

177. Emgality [prescribing information]. Indianapolis, IN: Eli Lilly and Company; 2018.

178. Ajovy [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2018.

179. Clinicaltrials.gov. Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children (PUL). NCT02106351. Available at: https://clinicaltrials.gov/ct2/show/NCT02106351


Codes:

(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

    31513
    31570
    31573
    31571
    43201
    43236
    46505
    52287
64611
    64612
    64615
    64616
    64617
    64640
    64642
    64643
    64644
    64645
    64646
    64647
    64650
    64653
    67345
    95873
95874


HCPCS
    J0585
    J0586
    J0587
    J0588

* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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