LCD L39836: Botulinum Toxin Injections

General Indications and Limitations of Coverage

• Botulinum toxin dosing must be used in accordance with the United States Food and Drug Administration (FDA) approved labeling.

• For off-label botulinum toxin use without an FDA approved dosing indication, the qualified healthcare professional must provide robust published clinical evidence to support the dosing use.

• For off-label botulinum toxin use without an FDA approved serotype indication, the qualified healthcare professional must provide robust published clinical evidence to support the serotype use.

• For new FDA approved indications for botulinum toxin serotype or dosing recommendations after the effective date of this policy, the qualified healthcare professional must provide the updated published FDA prescribing information to support the use of the botulinum toxin serotype or dose.

• Botulinum toxin administration must not be given more frequently than every 12 weeks, regardless of diagnosis, unless specifically addressed in the policy.

• The use of botulinum toxin for all cosmetic procedures is not a covered benefit under Medicare; AND

• When botulinum toxin is used for an approved diagnosis, but the botulinum is also being used with cosmetic intent, the entire claim for the botulinum is not considered reasonable and necessary, AND

• The potency of each of the botulinum toxin serotypes are not interchangeable with other botulinum toxin serotypes and, therefore, units of biological activity of any 1 serotype cannot be compared to or converted into units of any other botulinum toxin serotype; AND

• Botulinum toxin injections (BTIs) are not considered reasonable and necessary for patients with a contraindication to botulinum toxin; AND

• BTIs are not considered reasonable and necessary for patients with existing medical conditions which could affect the neuromuscular function; AND

• BTIs are not considered reasonable and necessary for patients with hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation of the serotype; AND

• BTIs are not considered reasonable and necessary for patients with severe clotting disorders; AND

• BTIs are not considered reasonable and necessary for patients with an infection at the injection site; AND

• Both conscious sedation and monitored anesthesia care (MAC) are not medically necessary for BTIs; AND

• When conservative treatment needs to be provided prior to the administration of botulinum toxin, a vague or nonspecific physician statement that conservative treatment measures were completed is not sufficient. The documentation must provide specific information regarding the conservative treatments which were used and an objective assessment of the intolerance or inadequacy of the response to the conservative measures.

• Image guidance is not considered reasonable and necessary for injection of botulinum toxin.

• Medicare will allow payment for 1 injection per site regardless of the number of injections made into the site. A site is defined as 1 area.

Specific Indications and Limitations of Coverage by Diagnosis

Achalasia

Definition:

Achalasia is a relatively rare primary motor esophageal disorder, characterized by incomplete relaxation of the esophageal gastric junction (EGJ) coupled with the absence of organized peristalsis along the esophageal body. Three achalasia subtypes have been defined based on the high-resolution manometry (HRM) findings in the esophageal body: type I or classic achalasia with low intraesophageal pressure, type II with pan-esophageal pressurization, and type III with high-amplitude spastic contractions.

Diagnosis:

The diagnostic criterion for achalasia is evaluated by HRM, which is recognized as the gold standard for diagnosis. 1,2 HRM measures the integrated relaxation pressure (IRP) at the EGJ, with an IRP greater than 15 mmHg serving as a critical diagnostic marker for achalasia. The Chicago Classification system enables the categorization of achalasia into 3 distinct subtypes based on the IRP and esophageal pressurization patterns observed during swallowing. Each subtype has specific clinical implications and guides the management strategy, with type II achalasia generally associated with the most favorable treatment outcomes. 1,2

Treatment:

BTI is an FDA off-label use consisting of endoscopic injections of the toxin into 4 quadrants of the lower esophageal sphincter (LES). The treatment options in achalasia patients aim to improve symptoms by reducing the functional obstruction at the level of the gastroesophageal junction. Injection of botulinum toxin reduces LES pressure by inhibiting release of acetylcholine from nerve endings. 3-9

Indications of Coverage

Initial Botulinum Toxin Injections

In the management of achalasia, BTI is an FDA off-label use consisting of endoscopic injections of the toxin into 4 quadrants of the LES. 3-9 Initial BTIs for achalasia will be considered reasonable and necessary when the following requirements are met:

• Objective documentation of the clinical features consistent with the diagnosis of achalasia; AND

• Chronic achalasia measured on objective clinical scale*; AND

• Medically high-risk patients diagnosed with achalasia who cannot undergo other invasive treatments (peroral endoscopic myotomy (POEM), Heller myotomy, pneumatic dilation [PD]); 1,2,8,10-15 OR

• As a bridge for those patients diagnosed with achalasia awaiting more effective treatments such as Heller myotomy, PDs or POEM; 2 OR

• During work-up and treatment planning of definitive treatments for achalasia. 16,17

* The objective assessment must be performed and documented at baseline, after each diagnostic procedure, and at each follow-up assessment using the same scale during each assessment. There are several clinical scales to measure severity of achalasia, for example the Eckert Scale.

Initial Dosing Guidelines

• The initial dose of onabotulinumtoxinA is 80 to 100 Units.

Subsequent Botulinum Toxin Injections

Subsequent BTIs for achalasia will be considered reasonable and necessary when the following requirements are met:

• Documentation of informed clinical decisions regarding repeat botulinum toxin injections; AND

• Reassessment of the degree of persistent moderate to severe achalasia; AND

• There is evidence of a significant beneficial symptomatic response to the initial dose.

Subsequent Dosing Guidelines

• The subsequent dose of up to 100 Units onabotulinumtoxinA may be given 30 days after the initial dose.

Limitations of Coverage

BTIs are not considered reasonable and necessary for:

• The patient who has achalasia symptoms but insufficient manometric criteria to make the diagnosis.

• Patients with contraindications for upper endoscopy. 18

• Injection of botulinum toxin in the esophageal body . 1,2,8,13

• Initial or subsequent onabotulinumtoxinA doses above 100 Units. 1,2

Anal Fissure

Definition:

A linear tear in the anal mucosa typically extending into the internal anal sphincter. Anal fissures that persist for more than 6 weeks are classified as chronic. The internal sphincter spasm is believed to be the main etiology for the pathogenesis of chronic anal fissure. 19

Diagnosis:

Anal fissures are characterized by a longitudinal linear tear primarily caused by trauma or irritation from constipation or diarrhea. 20 Fissures are commonly located in the posterior midline. Variations in location, such as anterior midline or atypical lateral positions, necessitate a thorough evaluation due to potential underlying conditions. 20

Chronic fissures exhibit additional features such as a hypertrophied anal papilla, a sentinel tag, and possibly exposed internal anal sphincter muscle, indicative of underlying issues like sphincter hypertonicity and impaired wound healing. This distinction is crucial for diagnosis and treatment, as chronic fissures may display additional physical features such as a hypertrophied anal papilla at the proximal edge of the fissure, a sentinel tag (or skin tag) at the distal edge, and exposure of the internal anal sphincter muscle at the base of the fissure, indicating a more complex condition requiring specialized management strategies. 20

Indications of Coverage

Initial Botulinum Toxin Injections

Initial BTIs for anal fissure will be considered reasonable and necessary when the following requirements are met:

• The anal fissure has been present for more than 6 weeks; AND

• Conservative treatment has been tried for eliminating constipation and reducing anal sphincter spasm.

Initial Dosing Guidelines

• The initial treatment with onabotulinumtoxinA dosing for anal fissure is 20 Units (10 Units on each side of the fissure). 21,22

Subsequent Botulinum Toxin Injections

Subsequent BTIs for anal fissure will be considered reasonable and necessary when the following requirements are met:

• Documentation for informed clinical decision-making regarding repeat BTIs and surgical treatment; AND

• Reassessment of the symptoms and degree of persistent anal fissure.

Subsequent Dosing Guidelines

• A subsequent dose of onabotulinumtoxinA for anal fissure is up to 60 Units with the clinical trials demonstrating greater efficacy with lower doses. 20

Blepharospasm

Definition:

A focal dystonia involving the involuntary closure of the eyelids and spasms of the orbicularis oculi muscles characterized by sustained or intermittent muscle contractions resulting in mild blinking or sustained forced closure of the eyes.

Diagnosis:

To diagnose a patient with blepharospasm, clinicians should observe for involuntary contraction of the orbicularis oculi and other muscles involved in eyelid closure, which can range from sporadic and mildly irritating to functionally blinding. 23 The disorder often begins with infrequent bilateral eyelid twitching and may progress to forceful and frequent spasms, including symptoms like eyelid apraxia. Sensory stimulation such as touching the eyelids or certain activities may temporarily reduce the contractions.

Diagnosis is primarily clinical and considered a diagnosis of exclusion, with imaging or laboratory studies typically not indicated. The diagnostic criteria for blepharospasm have been proposed, with key features being bilateral spasms of the orbicularis oculi and nearby muscles of the upper face often with excessive blinking. 23 Clinicians may encounter patients presenting with associated symptoms such as anxiety, depression, or ocular surface diseases like blepharitis. 4 Differential diagnosis includes distinguishing from conditions like Meige syndrome, myokymia, hemifacial spasm, and others based on the symmetry, distribution, and accompanying symptoms. Photophobia and response to sensory triggers are common, and the patient's history of triggers and symptom progression is essential for accurate diagnosis. To accurately diagnose blepharospasm without inadvertently diagnosing Meige Syndrome, it's essential to focus on the primary symptom of involuntary eyelid closure, ensuring it is bilateral, synchronous, and stereotyped, without the presence of significant lower facial or neck muscle involvement. 23

Despite this focal blepharospasm being the second most common type of dystonia, a high percentage of individuals given this diagnosis had dystonia outside of the eye/upper face region 5 which makes the diagnosis inconsistent with existing guidelines for the diagnosis and classification of focal blepharospasm. These authors proposed that the diagnosis of focal blepharospasm be based on dystonic spasms of muscles in the upper face around the eyes only.

The most sensitive findings to diagnose blepharospasm is a stereotypical bilateral and synchronous orbicularis oculi muscle spasms inducing eyelid narrowing closure, the presence of a sensory trick (the sensory trick was defined as any kind of maneuver performed by the patient that led to a transient reduction in spasm severity in the period of time immediately after its execution 24 ), and increased blinking. 4 Blepharospasm can be classified into idiopathic, acquired, and inherited subtypes. 25

The rating instruments in the medical literature have coalesced into several main clinical scales, including the Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). 26

Indications of Coverage

Initial Botulinum Toxin Injections

Initial BTIs for blepharospasm will be considered reasonable and necessary when the following requirements are met:

• Objective documentation of the clinical features consistent with the diagnosis of blepharospasm; AND

• Chronic blepharospasm of at least 30 days duration measured using an objective clinical scale*; AND

• BTI therapy is accepted first line treatment for patients with blepharospasm.

* The objective assessment must be performed and documented at baseline, after each diagnostic procedure, and at each follow-up assessment using the same scale during each assessment. For example, there are several clinical scales to measure severity of blepharospasm, including the JRS and BSDI.

Initial Dosing Guidelines

• The initial treatment with onabotulinumtoxinA dosing for blepharospasm associated with dystonia is 1.25 Units-2.5 Units into each of 3 sites per affected facial or ocular muscle. 27

Subsequent Botulinum Toxin Injections

Subsequent BTIs for blepharospasm will be considered reasonable and necessary when the following requirements are met:

• Documentation of informed clinical decisions regarding repeat BTIs; AND

Achalasia

Society Guidelines

We found 3 guidelines issued by medical societies and 1 position statement: the American Society of Gastroenterology (ASGE)’s Guideline on the Management of Achalasia 2020 13 , the International Society for Diseases of the Esophagus ( ISDE)’s 2018 Achalasia Guidelines 2 , the American College of Gastroenterology (ACG) Clinical Guidelines for the Diagnosis and Management of Achalasia, 2020 8 , and the European Society of Gastrointestinal Endoscopy ( ESGE) Guideline 2020 1 support BTI into the distal esophageal sphincter as an effective short-term treatment for achalasia, in medically high-risk patients who are not candidates for other invasive therapies.

The ASGE guidelines 13 were based on a systematic review and meta-analysis by Khashab et al. (2020). The review included 22 uncontrolled studies (published from inception to October 2017) in 730 achalasia patients who were treated with BTI. Clinical success, defined by an Eckardt score of 3, was achieved in 77% (95% confidence interval [CI], 72%-81%; I 2 value 35; P= 0.04) over a follow-up period ranging from 1 to 6 months. There was a statistically significant decrease in average LES pressure from 38.23 mm Hg (range, 34.40-42.06) before the procedure to 23.30 mm Hg (range, 20.79-25.81) after BTI (P The ESGE 1 performed a systematic review (discussed below under the systematic review by Weusten et al. (2020)) and Delphi consensus and aligned with previous recommendations. They additionally made specific dosing recommendations of 100 units onabotulinumtoxinA or equivalent of the toxin diluted in preservative-free saline that is injected in aliquots of 0.5–1mL using an injection needle in forward view just above the squamocolumnar junction in at least 4 quadrants. This was a strong recommendation, high quality of evidence, with a level of agreement of 100%. A multicenter randomized trial with injections of 50, 100, and 200 Units of BTI resulted in similar short-term results in LES pressure 1 month after injection 11 and in an SR, a dose of 100 units of botulinum toxin was used most frequently 77 , supporting this dosing recommendation.