Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Repository Corticotropin (H.P. Acthar® Gel Injection)

Policy #:08.01.12b

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

WEST SYNDROME
Repository corticotropin (H.P. Acthar® Gel Injection) for West Syndrome (infantile spasms) is considered medically necessary and, therefore, covered for a period of 12 months when both of the following criteria are met:
  • Individual is diagnosed with West Syndrome (infantile spasms).
  • Individual is two years of age or younger.

In accordance with FDA-approved prescribing information labeling, repository corticotropin (H.P. Acthar® Gel Injection) dosing for the treatment of West Syndrome (infantile spasms) is as follows:
  • Dosage should be given via intramuscular injections of 75 U/m2 twice daily.
  • Dosing should be tapered after 2 weeks and eventually discontinued over a 2-week period in order to avoid adrenal insufficiency.
  • Tapering schedule: 30 U/m2 in the morning for 3 days, 15 U/m2 in the morning for 3 days, 10 U/m2 in the morning for 3 days, then 10 U/m2 every other morning for 6 days.

NOT MEDICALLY NECESSARY

MULTIPLE SCLEROSIS
The Company's products contain a definition of medical necessity that includes a requirement that a service not be more costly than an alternative service that is at least as likely to produce equivalent therapeutic or diagnostic results for the treatment of that individual's illness. Repository corticotropin (H.P. Acthar Gel Injection) is considered not medically necessary and, therefore, not covered for the treatment of acute exacerbations of multiple sclerosis since it is more costly than an alternative service that is at least as likely to produce equivalent therapeutic results for that individual's illness.

OTHER INDICATIONS
Coverage for repository corticotropin (H.P. Acthar Gel Injection) for the treatment of additional indications on the prescribing label may depend upon the Company's applicable health benefit plan definition of medical necessity. The Company's products contain definitions of medical necessity that include a requirement that a service be covered in accordance with generally accepted standards of medical practice. Generally accepted standards of medical practice means standards that are based on all of the following:
  • Credible scientific evidence, published in peer-reviewed medical literature that is generally recognized by the relevant medical community
  • Physician specialty society recommendations
  • Views of physicians practicing in relevant clinical areas
  • Other relevant factors

Because repository corticotropin (H.P. Acthar Gel Injection) for the treatment of conditions other than West Syndrome are not based on generally accepted standards of medical practice and does not meet the requirement of a service not be more costly than an alternative service that is at least as likely to produce equivalent therapeutic or diagnostic results to the treatment of that individual's illness, repository corticotropin (H.P. Acthar Gel Injection) is considered not medically necessary for additional indications under those benefit plans. Some examples of indications that are considered not medically necessary and, therefore, not covered are:
  • Rheumatic disorders: psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis
  • Collagen disease: systemic lupus erythematosus, systemic dermatomyositis (polymyositis)
  • Dermatologic disease: severe erythema multiforme, Stevens-Johnson syndrome
  • Allergic states: serum sickness
  • Ophthalmic diseases: keratitis, iritis, iridocyclitis, diffuse posterior uveitis, choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation
  • Respiratory: symptomatic sarcoidosis
  • To induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
  • Corticosteroid-responsive conditions
  • Diagnostic testing for adrenocortical function

OFF-LABEL INDICATIONS
Repository corticotropin (H.P. Acthar Gel Injection) is considered not medically necessary and, therefore, not covered for any indications supported as an off-label indication, by the Company's medical policy on off-label coverage for prescription drugs and biologics due to the lack of supporting evidence of effectiveness and safety through controlled clinical studies or clinical practice guidelines.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for repository corticotropin (H.P. Acthar® Gel Injection) are considered experimental/investigational and, therefore, not covered because the indication is not supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

Individuals receiving repository corticotropin (H.P. Acthar® Gel Injection) for their condition may be trained by a professional provider to self-administer the medication at home. In addition, caregivers may also be trained by professional providers to administer the medication as necessary to individuals unable to self-administer repository corticotropin (H.P. Acthar® Gel Injection).

DRUG ADMINISTRATION

INFANTILE SPASMS
Repository corticotropin (H.P. Acthar® Gel Injection) should be gradually tapered over a 2-week period to avoid adrenal insufficiency. In accordance with the FDA-approved label, the suggested tapering schedule is 30 U/m2 in the morning for 3 days; 15 U/m2 in the morning for 3 days; 10 U/m2 in the morning for 3 days; and 10 U/m2 every other morning for 6 days.

OTHER INDICATIONS
Sudden withdrawal from repository corticotropin (H.P. Acthar® Gel Injection) after prolonged use may cause adrenal insufficiency or recurrent symptoms that make it difficult to stop treatment. It may be necessary to taper the dose and increase the injection interval to gradually discontinue repository corticotropin (H.P. Acthar® Gel Injection).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, repository corticotropin (H.P. Acthar® Gel Injection) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Repository corticotropin (H.P. Acthar® Gel Injection) was initially approved by the FDA in 1952. Supplemental approvals for repository corticotropin (H.P. Acthar® Gel Injection) have since been issued by the FDA.

Description

Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide hormone secreted by the anterior pituitary gland. ACTH is an agonist for the melanocortin receptor (MCR) system in the adrenal cortex. The binding of ACTH stimulates cortisol production and production of other hormones suppressing the body’s inflammatory process. The MCR system is a complex and expansive mechanism that may have more functions beyond inducing corticosteroid production. Repository corticotropin (H.P. Acthar® Gel Injection) is a purified preparation of the naturally occurring corticotropin polypeptide (ACTH) to provide a prolonged release after intramuscular or subcutaneous injection.

WEST SYNDROME

In 2010 the US Food and Drug Administration (FDA) revised the label for repository corticotropin (H.P. Acthar® Gel Injection) for monotherapy of infantile spasms, or West Syndrome, in individuals under two years of age. West Syndrome is a rare life-threatening form of epilepsy that typically begins in the first year of life. It is characterized by seizures, mental neurodevelopmental regression, and hypsarrhythmia findings on electroencephalograms. Spasms occur during the vulnerable development of a previously stressed or damaged central nervous system and continue periodically throughout development. One study cited by the FDA included 29 infants at the Children's Hospital of Los Angeles who were either placed on a 2-week regimen of high ACTH medication or given prednisone, a corticosteroid (Baram TZ et al.). The study showed that ACTH monotherapy causes a cessation of spasms and hypsarrhythmias over a 2-week period more effectively (87% of participants on ACTH monotherapy) than corticosteroid therapy (29% participants on corticosteroid therapy). The mechanism of action of repository corticotropin (H.P. Acthar® Gel Injection) for the treatment of infantile spasms is unknown.

MULTIPLE SCLEROSIS

In 1978, repository corticotropin (H.P. Acthar® Gel Injection) received FDA approval for the treatment of acute exacerbations of multiple sclerosis in adults. This approval was based on a double-blinded multicenter clinical study of 197 individuals published by Rose et al. Individuals were randomized to receive intramuscular injections of corticotropin or placebo during a 2-week hospitalization for acute exacerbations of multiple sclerosis. Results indicated there was beneficial effects in the corticotropin group compared to the placebo group. Reviews of this study found that the differences between the two study groups is less pronounced as the dosage of corticotropin was reduced during the second week of treatment.

The findings from several small studies from the 1980s compared the treatment of acute exacerbations of multiple sclerosis with ACTH (corticotropin) to intravenous methylprednisolone (IV-MP). They found there was no significant difference in effectiveness between the two therapies, but IV-MP had fewer side effects. The IV-MP group was shown to have a faster rate of improvement than the ACTH group within the first 3 days, but there is no significant difference in the final outcome after 3 months. Berkovich et al. reviewed the clinical studies and concluded more evidence is needed before a recommendation can be made to support the use of ACTH versus IV-MP. The Cochrane Collaboration published a systematic review of methylprednisolone or ACTH for acute exacerbations in multiple sclerosis. Six trials, published between 1961 and 1998, were included with a total of 377 individuals. Indirect comparisons suggest methylprednisolone has a significantly greater effect than ACTH for improving the rate of recovery from acute exacerbations of multiple sclerosis. Results from these clinical studies led to corticosteroid treatment becoming the standard of care for acute exacerbations of multiple sclerosis in conjunction with disease-modifying agents interferon beta-1a (Avonex®, Rebif®) or interferon beta-1b (Betaseron®).

OTHER CONDITIONS OR INDICATIONS

Repository corticotropin (H.P. Acthar® Gel Injection) received initial marketing approval from the FDA in 1952 before there was a requirement of clinical evidence of effectiveness. There was only a requirement to demonstrate safety. On October 10, 1962 the Kefauver-Harris Drug Amendments were signed into law. These amendments required drug manufacturers provide evidence of the effectiveness based on adequate and well-controlled clinical studies conducted by qualified experts before the FDA could approve the drug for market. Prior to this, while the FDA required that new drugs show safety, manufacturers could sell a drug if the FDA didn't act within 60 days to prevent its marketing. Due to repository corticotropin (H.P. Acthar® Gel Injection) receiving approval predating the Kefauver-Harris Drug Amendments there are indications on the prescribing label that has no supporting evidence of effectiveness. The prescribing information for repository corticotropin (H.P. Acthar® Gel Injection) includes the following additional broad indications:
  • Rheumatic disorders: as adjunctive therapy for acute exacerbations of psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis
  • Collagen disease: treatment of selected cases of systemic lupus erythematous and systemic dermatomyositis
  • Dermatologic disease: treatment of severe erythema multiforme and Stevens-Johnson syndrome
  • Allergic states: treatment for serum sickness
  • Ophthalmic diseases: treatment of severe acute and chronic allergic and inflammatory processes including optic neuritis, keratitis, and iritis
  • Respiratory disease: treatment of symptomatic sarcoidosis
  • Edematous state: treatment of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or due to lupus erythematosus

Although these indications are on the prescribing label there is no current clinically significant evidence on the effectiveness of repository corticotropin in these conditions. There is no proven non-inferiority or superiority of repository corticotropin when compared to corticosteroids. Based on available research, a clinically equivalent response that can be achieved with repository corticotropin may be achieved with an appropriate dose of corticosteroids with a lower risk of significant adverse events. Corticosteroids are considered standard of care across all the labeled indications unlike repository corticotropin which is not recommended in clinical practice guidelines or specialty medical societies. Alternative therapies are available to individuals non-responsive to corticosteroids. Some alternative therapies that have been discussed within the peer-reviewed literature, depending on the disorder, include plasmapheresis, intravenous immune globulin (IVIG), chlorambucil, mycophenolate, rituximab, cyclosporine, and tacrolimus.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Abbruzzese G, Gandolfo C, Loeb C. "Bolus" methylprednisolone versus ACTH in the treatment of multiple sclerosis. Ital J Neurol Sci. 1983;2:169-172.

American Hospital Formulary Service (AHFS). Drug Information. 2016. Corticotropin (Pituitary). [Lexicomp website]. Available http://online.lexi.com/lco/action/home. [via subscription only]. Accessed July 12, 2016.

Baram TZ, Mitchell WG, Tournay A, et al. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996;97(3):375-9.

Barnes M, Bateman D, Cleland P, et al. Intravenous methylprednisolone for multiple sclerosis in relapse. J Neurol Neurosurg Psychiatry. 1985;48:157-159.

Berkovich, Regina. Treatment of acute relapses in multiple sclerosis. Neurotherapeutics. 2013;10:97-105.

Citterio A, La Mantia L, Ciucci G, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database of Syst Rev. 2000;(4): CD001331.

Exacerbations. [The National MS Society]. Available at: http://www.nationalmssociety.org/Treating-MS/Managing-Relapses Accessed July 12, 2016.

FDA Acthar Gel NDA 22-432 Peripheral and Central Nervous System Drugs Advisory Committee Meeting. 05/06/2010. Available at:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM210503.pdf. Accessed July 12, 2016

Gettig J, et al. H.P. Acthar Gel and cosyntropin review. P&T. 2009;34(5):250-257. Also available on the NCBI Web site at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697107/. Accessed July 12, 2016.

Glauser, T. et al. Infantile spasms (West Syndrome). [Medscape Reference]. 10/16/2014. Available at: http://emedicine.medscape.com/article/1176431-overview. Accessed July 12, 2016.

Go C, Mackay M, Weiss S, et al. Evidence-based guideline update: Medical treatment of infantile spasms. Neurology. 2012; 78(24):1974-1980.

H.P. Acthar Gel (adrenocorticotropic hormone ACTH). [National Multiple Sclerosis Society]. Available at: http://www.nationalmssociety.org/Treating-MS/Medications?H-P-Acthar%c2%ae. Accessed July 12, 2016.

Hrachovy RA, et al. High-dose, long duration versus low-dose, short-duration corticotropin therapy for infantile spasms. J Pediatr. 1994;124(5):803-806.

Ioachimescu A, Hamrahian A. Diseases of the Adrenal Gland. [Cleveland Clinic]. 08/2010. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/diseases-of-the-adrenal-gland/. Accessed July 12, 2016.

Ito M, et al. Low-dose ACTH therapy for West Syndrome: Initial effects and long-term
outcome. Neurology. 2002;58(1):110-114.

Lexi-Drugs Compendium. Corticotropin. [Lexicomp Online Web site]. 07/05/2016. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 12, 2016.

Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004;62:1668-1681.

Mallinckrodt Pharmeceuticals. Prescribing Information for H.P. Acthar Gel Injection. [Acthar]. 01/2015. Available at: http://www.acthar.com/pdf/Acthar-PI.pdf. Accessed July 12, 2016.

Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937-1949.

Micromedex® Healthcare Series. DrugDex®.Corticotropin. [Micromedex® Web site]. Last modified: 06/02/2016. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 12, 2016.

Milanese C, La Mantia L, Salmaggi A et al. Double-blind randomized trial of ACTH versus dexamethasone versus methylprednisolone in multiple sclerosis bouts. Clinical cerebrospinal fluid and neurophysiological results. Eur Neurol. 1989; 29:10-14.

NINDS infantile spasms information page. [National Institute of Neurological Disorders and Stroke].11/03/2015. Available at: http://www.ninds.nih.gov/disorders/infantilespasms/infantilespasms.htm#What_is_the_prognosis. Accessed June 3, 2015.

Perrin Ross A, Ben-Zacharia A, Harris C, et al. Multiple Sclerosis, Relapses, and the Mechanism of Action of Adrenocorticotropic Hormone. Front Neurol. 2013; 4: 21. Published online 2013 March 8. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591751/. Accessed July 12, 2016.

Rose AS, Kuzma JW, Kurtzke JF, et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970;20(5):1-59.

Thompson A. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989;39:969-971.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Drug details: H.P. Acthar Gel (repository corticotropin) Injection. [FDA Web site]. 04/2016. Available at: http://www.accessdata.fda.gov/Scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory. Accessed July 12, 2016.






Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

G40.821 Epileptic spasms, not intractable, with status epilepticus

G40.822 Epileptic spasms, not intractable, without status epilepticus

G40.823 Epileptic spasms, intractable, with status epilepticus

G40.824 Epileptic spasms, intractable, without status epilepticus

P90 Convulsions of newborn



HCPCS Level II Code Number(s)

J0800 Injection, corticotropin, up to 40 units


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

08.01.12b
11/21/2018This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 07/01/2015
Version Issued Date: 07/01/2015
Version Reissued Date: 11/27/2018

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