Clinical Policy Title: Botulinum toxin products

Transcription

1 Clinical Policy Title: Botulinum toxin products Clinical Policy Number: Effective Date: September 1, 2013 Initial Review Date: May 13, 2013 Most Recent Review Date: May 19, 2017 Next Review Date: May 2018 Related policies: Policy contains: Botulinum toxins A and B. Involuntary muscle activity ocular, GI, urinary, and spasticity. Hyperhidrosis. Chronic migraine. Dysphonia. CP# CP# CP# CP# CP# Hyperhidrosis, treatment of Spine pain trigger point injection Invasive treatment for cervicogenic headache and occipital neuralgia Temporomandibular joint disorder Deep brain stimulation ABOUT THIS POLICY: AmeriHealth Caritas Iowa has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas Iowa s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas Iowa when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas Iowa s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas Iowa s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas Iowa will update its clinical policies as necessary. AmeriHealth Caritas Iowa s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas Iowa considers the use of botulinum neurotoxin (BTX) to be clinically proven and, therefore, medically necessary after documented failure of conservative therapy when the following criteria are met: Prevention of chronic migraine: - At least four hours duration and 15 days per month. - Failure of four drugs proven for migraine prophylaxis, with a 60-day trial each: antiepileptics (topiramate, sodium valproate); beta-blockers (metoprolol, propranolol, timolol); and tricyclic antidepressant (amitriptyline). Blepharospasm: - Intermittent or sustained closure caused by involuntary contractions of the 1

2 orbicularis oris. Achalasia and cardiospasm: - Failure of conventional treatments: upright after eating, achalasia wedge positioning, and proton pump inhibitors. - High risk of complications from pneumatic dilation or surgical myotomy. - Previous dilation or myotomy failure or epiphrenic diverticulum or hiatal hernia. Urinary incontinence in neurologic disease: - Adults or children with spinal cord disease (spinal cord injury [SCI] or multiple sclerosis [MS]). - Symptoms of overactive bladder (OAB). - Anti-muscarinic drugs were ineffective or poorly tolerated. Spasmodic torticollis (cervical dystonia): - Clonic and/or tonic contractions of multiple neck muscles. - Sustained head torsion and/or tilt with limited neck range of motion. - Duration > six months. - Alternate causes (chronic neuroleptic contractures, other neuromuscular disorders) ruled out. Limb spasticity: - Equinus varus in children with cerebral palsy (CP). - Hereditary spastic paraplegia. - Demyelinating central nervous system diseases: MS, adductor spasticity, pain control in children undergoing adductor lengthening surgery, children and adults with upper extremity spasticity. - Spastic hemiplegia: stroke or traumatic brain injury (TBI). Chronic anal fissure: - Failure to respond to conservative therapy: topical nitroglycerin or diltiazem. Focal primary hyperhidrosis: - Episodic sweating unresponsive to or intolerant of anticholinergics, beta-blockers, or benzodiazepines. - Topical aluminum chloride ineffective. Sialorrhea: - Refractory to pharmacotherapy. Facial myokymia and trismus: - Post-radiation. Hirschsprung s disease: - Internal sphincter achalasia post-endorectal pull-through. Upper extremity tremor: - Medically refractory. - Successful first BTX trial. OAB: - Urge incontinence, frequency, and urgency. 2

3 - Adults with inadequate response to anticholinergics. Limitations: All other uses of BTX are not medically necessary. Where FDA labeling requirements impose limitations for use, AmeriHealth Caritas Iowa coverage follows FDA guidelines. When coverage criteria for BTX therapy are met, approval consists of a maximum of four treatments in one year (one injection every three months or 90 days). If initial criteria are met and clinical benefit is obtained but its duration is less than 90 days, then up to six treatments per year (one every two months or 60 days) may be considered on a case-by-case basis. The off-label use of BTX in children less than age 2 years is not medically necessary, as evidence supporting its off-label use in this population is insufficient. Prior authorization requirements: See Appendix A on page 15 for additional information. Alternative covered services: Table 1. Comparator treatments from systematic reviews detailed on pages 5 to 9, where comparisons other than placebo were used and reported. Indication Alternatives Anal fissure Surgery or topical ointments. Spasticity Physical therapy. Splinting or casting. Systemic muscle relaxant drugs. Hyperhidrosis Anticholinergics, beta-blockers. Benzodiazepines. Surgical sympathectomy. Topical agents (aluminum chloride). Chronic migraine Anti-epileptics (topiramate, sodium valproate). Beta-blockers (metoprolol, propranolol, timolol). Tricyclic antidepressant (amitriptyline). Achalasia or cardiospasm Lifestyle or positioning: upright after eating, achalasia wedge positioning. Proton pump inhibitors. Pneumatic dilation or surgical myotomy. 3

4 Indication OAB Alternatives Anticholinergics Background Most widely known for its role in food poisoning (botulism), BTX is a culture-derived injectable toxin from the Clostridium botulinum bacterium that blocks acetylcholine release at the neuromuscular junction. In the late 1970s, interest in BTX emerged as a less invasive treatment for movement disorders and other conditions associated with increased cholinergic activity. BTX is injected directly into affected muscles to provide transient relief of symptoms. The paralytic effect is usually temporary, lasting approximately two to six months; recovery occurs when the affected axonal terminals sprout and reinnervate the muscle. Therefore, patients may require repeated injections to maintain treatment effects. BTX is classified into eight distinct serologically related neurotoxins. There are two main commercial types available for medical use: BTX type A (BTX-A) and BTX type B (BTX-B). Table 2 lists the four U.S. Food and Drug Administration (FDA)-approved BTX products for non-cosmetic use. Each product has a different dose-to-potency ratio, and the units of one product cannot be converted into units of another product (i.e., not interchangeable) (FDA, 2016; Appendix B). Table 2. FDA-approved BTX products Trade name New drug name Old drug name Dosage forms Botox (Allergan Inc., Irvine, California) Dysport (Ipsen biopharma ceuticals Inc., Basking Ridge, New Jersey) Xeomin (Merz Pharmaceuticals, Greensboro, North Carolina) Myobloc (Solstice Neurosciences Inc., Louisville, Kentucky) OnabotulinumtoxinA (onabtx-a) AbobotulinumtoxinA (abobtx-a) IncobotulinumtoxinA (incobtx-a) RimabotulinumtoxinB (rimabtx-b) Boxulinum toxin type A Boxulinum toxin type A Boxulinum toxin type A 100 unit, 200 unit vials 300 unit, 500 unit vials 50 unit, 100 unit vials Boxulinum toxin type B 5,000 units/ml (in 0.5 ml, 1 ml, 2 ml single-use vials) Searches AmeriHealth Caritas Iowa searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). 4

5 We conducted searches on March 15, Search terms were: "botulinum toxins" (MeSH) and freetext terms botox, myobloc, xeomin, and disport. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings While most, but not all, reviews identified at least some randomized controlled trials (RCTs), the trials were small, underpowered, or otherwise subject to bias. Some trials found unacceptably high adverse event rates, including those leading to early termination. Important unresolved research questions include optimal doses, treatment intervals, criteria for retreatment, and direct comparisons with other treatments. Ethical and cost issues relate to the need for lifelong repeated injections versus less-invasive or potentially harmful alternatives. Policy updates: In 2015, we identified two new systematic reviews for this policy. One found strong evidence of safety and efficacy from 12 RCTs supporting the use of (abobtx-a) treatment in adult patients with upper limb spasticity caused by stroke (Dashtipour, 2015). The other review found some evidence of effectiveness from eight RCTs for BTX-A injections of trigger points for myofascial pain; however, further clinical trials should account for minimizing placebo effect, repeated dosing, adequate coverage of trigger points, and using ultrasound confirmation and guidance to provide conclusive evidence (Zhou, 2014). In 2016, we identified three new systematic reviews for this policy (Chen, 2015; Cui, 2015; Wu, 2015). Two reviews found insufficient evidence to determine the therapeutic benefits of BTX for temporomandibular joint disorders (TMDs) or shoulder pain (Chen, 2015; Wu, 2015). Cui (2015) found onabtx-a a safe and effective treatment for idiopathic OAB compared to placebo-controlled studies. These findings would not change earlier conclusions. However, the FDA has approved a new indication for incobtx-a (Xeomin) for treatment of upper limb spasticity in adults. Treatment is limited to a total dose of up to 400 units no more frequently than every 12 weeks (Appendix B). In 2017, we added two new systematic reviews (Alviar, 2016; Morra, 2016), a Cochrane review update 5

6 (Duarte, 2016), and an updated evidence-based guideline from the American Academy of Neurology (AAN) (Simpson, 2016). Alviar et al. identified only one, small RCT of BTX-A for treatment of phantom limb pain. For treating trigeminal neuralgia, results from four small RCTs found a positive effect for BTX- A compared with placebo (Morra, 2016). Results from these reviews remain inconclusive due to the paucity of evidence for both indications. The most recent Cochrane review update found that a single treatment session of either onabtx-a (100 U to 250 U) or rimabtx-b (5,000 U to 10,000 U) is equally effective and safe in adults with certain types of cervical dystonia, which is consistent with the previous findings of this policy (Duarte, 2016). The AAN s updated recommendations for blepharospasm, cervical dystonia, adult spasticity, and headache are also consistent with this policy (Simpson, 2016). Therefore, no policy changes are warranted at this time. Summary of clinical evidence: Citation Alviar (2016) Cochrane review Phantom limb pain Duarte (2016) Cochrane review Cervical dystonia Morra (2016) BTX-A for trigeminal neuralgia Simpson (2016) for the American Academy of Neurology Content, Methods, Recommendations Systematic review of 14 studies (269 total participants), including one study of BTX-A. Overall quality: low or unclear risk of bias with small sample size. Inconclusive evidence for short- and long-term effectiveness of BTX-A, opioids, N-methyl D- aspartate receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anesthetics for clinically relevant outcomes. Systematic review and meta-analysis included three RCTs (270 total participants). Overall quality: very low to low with a high risk of bias. A single treatment session of either onabtx-a (100 U to 250 U) or rimabtx-b (5,000 U to 10,000 U) is equally effective and safe in the treatment of adults with certain types of cervical dystonia. RimaBTX-B may present an increased risk of sore throat/dry mouth, compared to onabtx-a, but no preference for one botulinum toxin over another can be made. Systematic review and meta-analysis of four RCTs (178 total patients). Proportion of responders favored BTX-A versus placebo (risk ratio = 2.87, 95% confidence interval [CI] 1.76 to 4.69, p < ); no significant heterogeneity (p = 0.31; I 2 = 4%). Paroxysms frequency/day was significantly lower for BTX-A group (mean difference , 95% CI to , p < ) with no significant heterogeneity (p = 0.21; I 2 = 36%). Results suggest that BTX-A may be effective and safe for patients with TN, but larger and welldesigned RCTs are needed. Blepharospasm: onabtx-a and incobtx-a probably effective and should be considered (Level 6

7 Citation Practice guideline update summary: BTX for blepharospasm, cervical dystonia, adult spasticity, and headache Chen (2015) BTX for TMDs Cui (2015) OAB Dashtipour (2015) AboBTX-A in adults with upper limb spasticity (ULS) Wu (2015) BTX for shoulder pain Chen (2014) Content, Methods, Recommendations B). AboBTX-A possibly effective and may be considered (Level C). Cervical dystonia: abobtx-a and rimabtx-b established as effective and should be offered (Level A); onabtx-a and incobtx-a probably effective and should be considered (Level B). Adult spasticity: abobtx-a, incobtx-a, and onabtx-a established as effective and should be offered (Level A): - For upper limb spasticity, rimabtx-b probably effective and should be considered (Level B). - For lower-limb spasticity, abobtx-a and onabtx-a established as effective and should be offered (Level A). Headache: onabtx-a established as effective and should be offered to increase headachefree days (Level A); probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine; established as ineffective and should not be offered for episodic migraine (Level A), and probably ineffective for chronic tension-type headaches (Level B). Systematic review of five relevant study trials (117 patients). Overall quality: low-to-moderate. Heterogeneous methods. Conflicting results. Unclear therapeutic benefits of BTX on TMDs versus placebo or any other intervention. Systematic review and meta-analysis of eight RCTs (1,320 patients), including six RCTs that compared onabtx-a with placebo. OnaBTX-A is an effective treatment for idiopathic OAB symptoms with side effects primarily localized to urinary tract. Systematic review of 12 RCTs and other comparative studies published between 1991 and January Overall quality: moderate to high. Total abobtx-a doses ranged between 500 and 1,500 U. Generally well tolerated. Statistically significant reduction in muscle tone based on Ashworth score of ABOBTX-A versus placebo, spasticity using the Modified Ashworth Scale and in active movement and pain. Systematic review of nine RCTs comparing BTX to steroid injection or placebo. Overall quality: unclear. Significant heterogeneity in designs limits conclusions. Compared to control, BTX injections improved pain scores and range of motion in adult patients with shoulder pain. Higher quality studies needed. BTX versus lateral internal sphincterotomy for anal fissure Seven RCTs (489 subjects). Surgery superior for healing and recurrence; but BTX has lower incontinence and wider applicability for poor surgical candidates. 7

8 Citation Zhou (2014) BTX-A for myofascial pain syndrome Baker (2013) Spasticity and pain in adults Fedorowicz (2013) Cochrane review Masseter hypertrophy Jackson (2012) Migraine and tension headache in adults Maltese (2012) for the Swedish Health Technology Assessment Agency Axillary and palmar hyperhidrosis Nelson (2012) Cochrane review Chronic anal fissure Rodwell (2012) Sialorrhea (drooling) in children with CP Content, Methods, Recommendations Systematic review of eight double-blinded RCTs. Overall quality: high. BTX-A is efficacious for myofascial pain syndrome. Further clinical trials need to address minimizing placebo effect, repeated dosing, adequate coverage of trigger points, and using ultrasound confirmation and guidance. Systematic review and meta-analysis of 37 RCTs published through April 2013; 10 in metaanalysis. No significant effects for BTX in upper limb spasticity; no effect for lower limb. Moderate evidence for spasticity. Spasticity-associated pain too inconsistently reported for analysis. Systematic review of RCTs and controlled clinical trials of BTX versus placebo published through April No eligible studies identified. Systematic review of 27 RCTs (5,423 subjects). BTX-A associated with greater benefit for chronic tension headaches, but limitations for conclusions on migraine and chronic daily headaches. Active comparator trials underpowered or otherwise subject to bias. Systematic review of 11 RCTs; one cohort; two case series. High-quality evidence (BTX-A versus placebo) for reduced sweat production; low quality (BTX- A versus aluminum chloride) for improved quality of life. Duration of effect, three months: ethical and cost issues. Systematic review of 54 RCTs (3,904 subjects and 5,032 comparisons) versus surgery, alternate medical therapy, nitroglycerin ointment, hydrocortisone, clove oil, or placebo, published through August Surgery superior to all medical treatments including BTX. Systematic review of 16 RCTs and prospective studies published through October Significant results for three outcomes (reduction in drooling, its impact and number of bibs required per day). Adverse effects: 2% to 41%, but inconsistently reported and one trial terminated early. 8

9 Citation Rowe (2012) Cochrane review Strabismus Naumann (2008) for the AAN (update in progress) Guideline: BTX for autonomic disorders and pain Costa (2005) Content, Methods, Recommendations Additional research needed: safety and direct comparisons with alternatives. Systematic review of four RCTs published through Two trials found no significant differences; two found varying results (poor response of horizontal strabismus, no response for acquired or infantile esotropia). Dose-effect and re-treatment information lacking. Recommendations for BTX treatment: - Should be offered for axillary hyperhidrosis and detrusor overactivity (Level A). - Should be offered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B). - May be considered for gustatory sweating and low back pain (Level C). - Probably ineffective in episodic migraine and chronic tension-type headache (Level B). - No consistent or strong evidence to support conclusions on the efficacy of BTX in chronic daily headache (mainly transformed migraine) (Level U). While clinicians' practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data. Cochrane review Hemifacial spasm Systematic review of one small RCT and several large observational series published from 1977 to Large range of benefits observed: outstanding issues include optimum treatment intervals, injection techniques and doses, and specific formulations. Specific comparisons with surgical microvascular compression needed. References Professional society guidelines/other: 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; 74(4): National Institute for Health and Clinical Excellence (NICE). Urinary incontinence in neurological disease. Management of lower urinary tract dysfunction in neurological disease. Clinical guideline no NICE website. Accessed March 16, Naumann M, So Y, Argoff CE, et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008; 70(19):

10 Practice guidelines for chronic pain management: an updated report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2010; 112(4): Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016; 86(19): Stefanidis D, Richardson W, Farrell TM, et al. SAGES guidelines for the surgical treatment of esophageal achalasia. Surg Endosc. 2012; 26(2): Peer-reviewed references: Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2016; 10: Cd Baker JA, Pereira G. The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach. Clin Rehabil. 2013; 27(12): Chen HL, Woo XB, Wang HS, et al. Botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure: a meta-analysis of randomized control trials. Tech Coloproctol. 2014; 18(8): Chen YW, Chiu YW, Chen CY, Chuang SK. Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials. Int J Oral Maxillofac Surg. 2015; 44(8): Comella CL, Jankovic J, Shannon KM, et al. Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology. 2005; 65(9): Costa J, Espmrito-Santo Claudia C, Borges Ana A, et al. Botulinum toxin type A therapy for hemifacial spasm. Cochrane Database of Systematic Reviews. 2005(1): CD Cui Y, Wang L, Liu L, et al. Botulinum toxin-a injections for idiopathic overactive bladder: a systematic review and meta-analysis. Urol Int. 2013; 91(4): Cui Y, Zhou X, Zong H, Yan H, Zhang Y. The efficacy and safety of onabotulinumtoxina in treating idiopathic OAB: A systematic review and meta-analysis. Neurourol Urodyn. 2015; 34(5):

11 Dashtipour K, Chen JJ, Walker HW, Lee MY. Systematic literature review of abobotulinumtoxina in clinical trials for adult upper limb spasticity. Am J Phys Med Rehabil. 2015; 94(3): Drugs@FDA. FDA approved drug products. FDA website. Accessed April 19, Duarte GS, Castelao M, Rodrigues FB, et al. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev. 2016; 10: Cd Fedorowicz Z, van Zuuren EJ, Schoones J. Botulinum toxin for masseter hypertrophy. Cochrane Database Syst Rev. 2013; 9: CD Jackson JL, Kuriyama A, Hayashino Y. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. JAMA. 2012; 307(16): Maltese K, Ryndel M, Alm-Dalgren J, et al. Botulinum toxin treatment of axillary and palmar hyperhidrosis. [Botulinum toxin behandling av axillär och palmar hyperhidros]. HTA-report 2012; 45. Salgrenska University Hospital HTA-centre website. AccessedMarch 16, Nelson RL, Thomas K, Morgan J, Jones A. Non-surgical therapy for anal fissure. Cochrane Database Syst Rev. 2012; 2: CD Regan J, Murphy A, Chiang M, McMahon Barry P, Coughlan T, Walshe M. Botulinum toxin for upper esophageal sphincter dysfunction in neurological swallowing disorders. Cochrane Database Syst Rev. 2014; 5: CD Rodwell K, Edwards P, Ware RS, Boyd R. Salivary gland botulinum toxin injections for drooling in children with cerebral palsy and neurodevelopmental disability: a systematic review. Dev Med Child Neurol. 2012; 54(11): Rowe FJ, Noonan CP. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev. 2012; 2: CD Wu T, Fu Y, Song HX, et al. Effectiveness of Botulinum Toxin for Shoulder Pain Treatment: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil. 2015; 96(12): Zhou JY, Wang D. An update on botulinum toxin A injections of trigger points for myofascial pain. Curr Pain Headache Rep. 2014; 18(1): 386. CMS National Coverage Determinations (NCDs): 11

12 No NCDs identified as of the writing of this policy. Local Coverage Determinations (LCDs): A53015 Botulinum Toxin Types A and B Coding Guidelines. CMS website. A53014 Botulinum Toxin Types A and B Policy Article: OnabotulinumtoxinA for Detrusor Muscle Treatment Billing/Coding Guidelines. CMS website. A54971 Botulinum toxins revision to the Part A and Part B LCD (J0585, J0588). CMS website. A52381 Botulinum Toxins - Supplemental Instructions Article. CMS website. A52848 Botulinum Toxins - Supplemental Instructions Article. CMS website. A54937 Botulinum Toxins revision to the LCD. CMS website. A55123 Botulinum toxins revision to the Part A and Part B LCD. CMS website. A55383 Response to Comments: Botulinum Toxin Types A and B. CMS website. A55384 Response to Comments: Botulinum Toxin Types A and B. CMS website. L34635 Botulinum Toxin Type A & Type B. CMS website. 12

13 L33274 Botulinum Toxins. CMS website. L33458 Chemodenervation. CMS website. L33646 Botulinum Toxins. CMS website. L33944 Blepharoplasty. CMS website. L33949 Botulinum Toxins. CMS website. L34253 Drugs and Biologicals: Botulinum Toxins. CMS website. L34528 Blepharoplasty, Blepharoptosis and Brow Lift. CMS website. L34635 Botulinum Toxin Type A & Type B. CMS website. L35170 Botulinum Toxin Types A and B Policy. CMS website. L35172 Botulinum Toxin Types A and B. CMS website. L35172 Botulinum Toxin Types A and B. CMS website. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comment Laryngoscopy; indirect; with vocal cord injection 13

14 CPT Code Description Comment Laryngoscopy; direct with injection in to the vocal cord(s) Laryngoscopy; direct with injection into vocal cord(s) with operating microscope Esophagoscopy, rigid, transoral; with directed submucosal injection(s), any substance Esophagoscopy, flexible, transoral, with directed submucosal injection(s), any substance EGD, flexible, transoral; with directed submucosal injection(s), any substance EGD, flexible, transoral, with ultrasound-guided transmural injection(s) of diagnostic or therapeutic substance Chemodenervation of internal anal sphincter Cystourethroscopy with injection(s) for chemodenervation of the bladder Chemodenervation of parotid and submandibular glands, bilateral Chemodenervation of muscles innervated by facial nerve, eg., blepharospasm Chemodenervation of muscles innervated by facial, trigeminal, cervical spinal and accessory nerves, eg, chronic migraine Chemodenervation of neck muscles, excluding larynx muscles, eg, cervical dystonia, spasmodic torticollis Chemodenervation of larynx, unilateral, percutaneous for spasmodic dystonia Chemodenervation of eccrine glands, bilateral ICD-10 Code Description Comment G24.3 Spasmodic torticollis G24.5 Blepharospasm G Chronic migraine without aura, not intractable, with status migrainosus G Chronic migraine without aura, not intractable, without status migrainosus G Chronic migraine without aura, intractable, with status migrainosus G Chronic migraine without aura, intractable, without status migrainosus G51.2 Melkersson's syndrome G51.3 Clonic hemifacial spasm G51.4 Facial myokymia G51.8 Other disorders of facial nerve G51.9 Disorder of facial nerve, unspecified K11.7 Disturbances of salivary secretion K22.0 Achalasia of cardia K60.0 Acute anal fissure K60.1 Chronic anal fissure K60.2 Anal fissure, unspecified L Primary focal hyperhidrosis, axilla L Primary focal hyperhidrosis, face L Primary focal hyperhidrosis, palms L Primary focal hyperhidrosis, soles L Primary focal hyperhidrosis, unspecified M M62.49 Contracture of muscle M Muscle spasm of calf 14

15 ICD-10 Code Description Comment M Other muscle spasm N32.81 Overactive bladder N Other specified urinary incontinence R68.2 Dry mouth, unspecified HCPCS Level II Code N/A Description Comment Appendix A AmeriHealth Caritas Iowa pharmacy prior authorization criteria for BTX products Field name Prior authorization group description Drugs Covered uses Exclusion criteria Required medical information Age restrictions Prescriber restrictions Coverage duration Other criteria Field Description Botulinum Toxins A&B OnabotulinumtoxinA (Botox ), IncobotulinumtoxinA (Xeomin ), AbobotulinumtoxinA (Dysport ), RimabotulinumtoxinB (Myobloc ) Medically accepted indications are defined using the following sources: the FDA, Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), the Drug Package Insert (PPI), or disease state specific standard of care guidelines. N/A N/A N/A None If all of the conditions are met, the request will be approved for a three-month duration. If the conditions are not met, the request will be sent to a Medical Director/clinical reviewer for medical necessity review. **The use of these medications for cosmetic purposes is NOT a covered benefit under the Medical Assistance program.** Botox is the preferred botulinum toxin for pediatric patients, chronic migraine, overactive bladder, and hyperhidrosis. Xeomin is the preferred botulinum toxin for spasmodic torticollis (cervical dystonia), blepharospasm, upper limb spasticity, and any other off-labeled indication that is supported or recommended by the medical compendia and standard of care guidelines. For approval: The request is for a FDA approved indication, and/or is used for a medical 15

16 Field name Revision/review date 11/2016 Field Description condition that is supported by the medical compendia and/or per standard of care guidelines in each respective disease state. Documentation was submitted, that the patient had an (consistent with pharmacy claims data) adequate trial (including dates of treatment at maximum recommended doses of therapy) of standard conventional first-line therapy for their respective disease state (where applicable) as recommended by the medical compendia and standard of care guidelines and/or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc.) for not taking standard conventional first line therapy to treat their medical condition. If the medication request is for Botulinum toxin type A (Botox) for treating Chronic Migraines ( 15 days per month with headache lasting four hours a day or longer), the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial of beta blockers (e.g. metoprolol, atenolol, nadolol, propranolol, timolol), tricyclic antidepressants (e.g., amitriptyline), Depakote, and topiramate, or a medical reason was submitted (intolerance, hypersensitivity, contraindication, etc.) why patient is not able to utilize these therapies. If the medication request is for Botulinum toxin type A (Botox) for treating Overactive Bladder, the patient has a documented treatment failure after receiving an adequate trial (consistent with pharmacy claims data) of at least two formulary medications (e.g., oxybutynin) If the medication is being requested for an off labeled use that is recommended by the medical compendia, the patient has a documented trial/failure (including dates) of Xeomin and/or has a medical reason (intolerance, hypersensitivity, contraindication, etc.) for not utilizing Xeomin to manage their medical condition Prescribed dosing of medication is within FDA-approved guidelines and/or is supported by the medical compendia as defined by the Social Security Act and/or per Standard of Care Guidelines in each respective disease state. Physician/clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. Appendix B FDA-approved and other medically accepted (non-cosmetic) uses for BTX products Onabotulinum toxin type A (Botox): Spasmodic torticollis (cervical dystonia) in adults (FDA-approved): To reduce the severity of abnormal head position and neck pain. 100 to 300 units (lower dose for patients without prior use of botulinum toxin to limit incidence of dysphagia) divided among affected muscles; limit total dose to 100 units or less may decrease the incidence of dysphagia. Response duration is up to three months. 16

17 Blepharospasm in patients 12 years (FDA-approved): 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 in a 30-day period should not exceed 200 units. Response duration is up to three months. Repeat treatments needed prior to three months are considered insufficient and the dose can be increased up to two-fold up to 5 units per site. Strabismus in patients 12 years (FDA-approved): - Initial doses: For vertical muscles and for horizontal strabismus of less than 20 prism diopters: units in any one muscle. For horizontal strabismus of 20 prism diopters to 50 prism diopters: units in any one muscle. For persistent VI nerve palsy of one month or longer duration: units in the medial rectus muscle. - Subsequent doses for residual or recurrent strabismus: Patients should be re-examined seven to 14 days after each injection to assess the effect of that dose. Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose comparable to the initial dose. Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to two-fold compared to the previously administered dose. The cumulative dose in a 30-day period should not exceed 200 units. Subsequent injections should not be administered until the effects of the previous dose have dissipated as evidenced by substantial function in the injected and adjacent muscles. The maximum recommended dose, as a single injection for any one muscle, is 25 units. Severe primary axillary hyperhidrosis inadequately managed by topical agents in adults (FDA-approved): The recommended dose is 50 units per axilla. Retreatment when clinical effect diminished. Chronic migraine (FDA-approved): For prophylaxis of headaches in adult patients with chronic migraine ( 15 days per month with headache lasting four hours a day or longer). The dose is 155 units administered intramuscularly (IM) as 5 units/0.1 ml per each site. Injections should be divided across seven specific head/neck muscle areas: frontalis, corrugator, procerus, occipitalis, temporalis, trapezius, cervical and paraspinal muscle group. All muscles should be injected bilaterally with half the number of injection sites administered to the left and half to the right side of the head and neck. Retreatment should occur every 12 weeks. OAB (FDA-approved): Treatment of OAB with symptoms of urge urinary incontinence, urgency and frequency or due to detrusor overactivity associated with a neurologic condition, in adults who have had an inadequate response to or are intolerant to 17

18 anticholinergic medication. OAB recommended total dose 100 units, as of 0.5mL (5 units) injections across 20 sites into the detrusor. For detrusor overactivity associated with a neurologic condition recommended total dose 200 units as 1mL (~6.7 units) injections across 30 sites into the detrusor. Retreatment when clinical effect of the previous treatment has diminished (no sooner than 12 weeks from prior bladder injection). Excessive salivation in Parkinson s, multiple system atrophy, neurological disorders, bulbar amyotrophic lateral sclerosis (adult and pediatric): Five to 30 units injected in divided doses into the parotid and submandibular glands at doses calculated by patient weight and rate of salivation. Response duration is from one to three months. Incontinence in SCI or trauma: units given as a single injection or monthly for two to three months. Single injection method response duration is about two to three months; monthly injection method response duration is nine to 13 months. Spastic dysphonia: Average dose of 10 units per side with higher doses up to 20 units required for abductor and adductor laryngeal involvement. Response duration is up to six months. Upper limb spasticity from cerebral vascular accident: units divided among affected muscles. Response duration is about 12 weeks. Upper limb spasticity from TBI: Dose depends on muscle injected. Doses range from 20 to 300 units injected in divided doses to affected muscles. Response duration is approximately four to six months. Lower limb spasticity from cerebral vascular accident or TBI: units injected in divided doses to affected muscle group. Response duration is eight to 12 weeks. Lower limb spasticity has inconclusive evidence on efficacy. Abducens nerve palsy: units injected into the medial rectus muscles. Response duration is from three to six months. Achalasia: units injected into the lower esophageal sphincter. Response duration is one year. Auriculotemporal syndrome (Frey s syndrome): 1 2 units per 2.25 cm 2 of hyperhidrotic skin as visualized by the iodine starch test. Total dose units; one to three sessions necessary. Response duration is from six to 12 months. Fibromyalgia: units injected into affected muscles. Response duration is up to two months. Hemifacial spasm: units divided among affected muscles. Response duration is from three to five months. Lower limb spasticity in MS: units divided among affected muscles per session. Response duration is from one to three months. CP: - For lower-limb spasticity, candidates for treatment with BTX include those with dynamic equinus persistent throughout the gait cycle, equinovarus deformity, a dynamic knee flexion angle exceeding 20 degrees during the gait cycle or one that 18

19 interferes with gait, or substantial scissoring and adduction at the hips. - For upper-limb spasticity, candidates for treatment with botulinum toxin include those with persistent thumb in palm or thumb adduction, wrist posture that prevents effective use or tight elbow flexion. - Dose: 1 8 units/kg divided among affected muscles. Response duration is typically one to three months. Myofascial pain syndrome: units depending upon the injected muscle. Response duration is based on relief of pain. Documentation must be submitted that the patient failed first-line therapy consisting of injections of local anesthetics and corticosteroids to trigger points, as well as massage, physical therapy and lifestyle changes to reduce stress. Oromandibular dystonia: For jaw-closing type use units into each masseter muscle. If satisfactory results are not obtained, 5 40 units may be injected into each temporalis muscle. Response duration is two to four months. Incobotulinum toxin A (Xeomin): Spasmodic torticollis (cervical dystonia) in adults (FDA-approved): The recommended total dose is 120 units per treatment session. Higher doses did not provide additional efficacy and were associated with an increased incidence of adverse reactions. Blepharospasm in adults (FDA-approved): In patients who have been previously treated with onabotulinumtoxina. When initiating treatment, the dose, number and location of injections should be based on the previous dosing of onabotulinumtoxina. If the previous dose of onabutlinumtoxina is not known, the recommended starting dose is units per injection site. In clinical trials, the mean dose per injection site was 5.6 units, the mean number of injections per eye was six and the mean dose per eye was 33.5 units. Upper limb spasticity in adults (FDA-approved): The recommended total dose is up to 400 units no more frequently than every 12 weeks. Abobotulinumtoxin A (Dysport): Spasmodic torticollis (cervical dystonia) (FDA-approved): 500 units given intramuscularly as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin. Doses above 1,000 units have not been systematically evaluated. Retreatment, if needed, should not occur in intervals of less than 12 weeks. RimabotulinumtoxinB (Myobloc): Spasmodic torticollis (cervical dystonia) (FDA-approved): 2,500 5,000 units divided among affected muscles in patients with a prior history of tolerating botulinum toxin. Patients without a prior history of tolerating botulinum toxin should receive a lower initial dose. The duration of effect in patients who responded to treatment (of doses of 5,000 10,000 units) in studies was 12 to 16 weeks. Severe primary axillary hyperhidrosis: units injected into 10 to 15 sites in each axilla. Doses as high as 5,000 units per axilla have been used. Response duration is two to 19

20 eight months (average is five months). Excessive salivation in Parkinson s: 1,000 units into each parotid gland, and 250 units into each submandibular gland. Response duration is up to 20 weeks. Incontinence in SCI: 5,000 units into detrussor muscle sites (trigone typically exempt). Response duration is up to one month. Spastic dysphonia: units into thyroarytenoid muscles; units to each vocal cord via the cricothyroid membrane. Response duration is up to 14 weeks. Upper limb spasticity from cerebral vascular accidents or traumatic brain injury: 5,000 17,500 total limb dose divided into specific muscles. Average of 375 2,500 for arm muscles. Response duration is four to 12 weeks. 20