Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

Description

Repository corticotropin injection (H.P. Acthar® Gel, Questcor, Union City, CA) is a purified sterile preparation of adrenocorticotropic hormone (ACTH) in gelatin to provide a prolonged release after intramuscular or subcutaneous injection. ACTH works by stimulating the adrenal cortex to produce cortisol, corticosterone, and a number of other hormones.
According to the product information (product labeling),repository corticotropin injection is indicated for the diagnostic testing of adrenocortical function. (1) This labeling information also notes that HP Acthar Gel “has limited therapeutic value in those conditions responsive to corticosteroid therapy, in such cases, corticosteroid therapy is considered to be the treatment of choice.” The product information notes that ACTH gel may be used in the treatment of the following conditions:

• Endocrine (nonsuppurative thyroiditis, hypercalcemia associated with cancer)
• Nervous system (acute exacerbations of multiple sclerosis)
• Rheumatic Disorders (as an adjunctive therapy for short-term administration in psoriatic arthritis, rheumatoid arthritis, etc.)
• Collagen Diseases (during an exacerbation or as maintenance therapy in systemic lupus erythematosus, dermatomyositis, etc.)
• Dermatologic Disease (pemphigus, bullous dermatitis herpetiformis, etc.)
• Allergic states (control of severe allergic conditions, etc.)
• Ophthalmic diseases (allergic conjunctivitis, etc.)
• Respiratory diseases (symptomatic sarcoidosis, Loeffler’s syndrome, etc.)
• Hematologic disorders (acquired autoimmune hemolytic anemia, etc.)
• Neoplastic diseases (palliative treatment of leukemias and lymphomas in adults, acute leukemia of childhood)
• Edematous state (nephrotic syndrome)
• Gastrointestinal diseases (ulcerative colitis, regional enteritis)
• Miscellaneous (tuberculous meningitis, trichinosis with neurologic or myocardial involvement)
  

Contraindications for use of this agent include scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, hypertension, or sensitivity to proteins of porcine origin.

Policy

Repository corticotropin injection may be considered medically necessary for use in diagnostic testing of adrenocortical function.

Repository corticotropin injection may be considered medically necessary for treatment of infantile spasms (West’s syndrome).

Use of repository corticotropin injection is considered not medically necessary as treatment of steroid-response conditions, unless there are medical contraindications or intolerance to corticosteroids that are not also expected to occur with use of repository corticotropin injection.

Except as noted above, use of repository corticotropin injection is considered investigational for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation, acute gout and childhood epilepsy.

Policy Guidelines

Repository corticotropin injection is one of the agents that can be considered for treatment of infantile spasms as noted in the Rationale section.
The product information material makes the following comments about dosage:

According to the manufacturer’s website, beginning in August 2007, H.P. Acthar Gel is only available through Specialized Pharmacy Distribution (i.e., no longer available from traditional pharmaceutical wholesalers or retail pharmacies). As of August 2009, the specialty pharmacy exclusive distribution is unchanged.

Benefit Application

Rationale

The policy was developed based on a literature search using MEDLINE in January 2008.

The literature search did not identify published articles that evaluated the use of repository corticotropin injection compared to use of corticosteroids in corticosteroid-responsive conditions. Use of repository corticotropin injection has the potential to cause more adverse effects. Thus, given this lack of comparative data and the statement in the product information-labeling, the clinical need (and clinical impact) to use repository corticotropin injection for steroid-responsive conditions has not been demonstrated. Thus, repository corticotropin injection in this clinical situation is considered not medically necessary.

West syndrome is considered a triad of infantile spasms, an EEG pattern called hypsarrhythmia, and mental retardation, although not all 3 components are required. Often the term infantile spasms is used synonymously with West syndrome. Infantile spasms are characterized by an initial contraction phase followed by a more sustained tonic phase. Repository corticotropin injection has been considered the first-line treatment for infantile spasms. Data for use of repository corticotropin injection was summarized in a practice parameter from the American Academy of Neurology. (2) While this review concluded that repository corticotropin injection is “probably an effective agent in the short-term treatment of infantile spasms” evidence for repository corticotropin injection was the stronger than for any other pharmacologic agent. The report also indicates that there is insufficient evidence to determine whether oral corticosteroids are effective, and that vigabatrin was possibly effective but that there are concerns about retinal toxicity. This report also notes that the impact of treatment of seizures/spasms on long-term patient outcomes is unknown.

Despite the first-line use of repository corticotropin injection for infantile spasms for many years, there are no medications that have FDA approval for this specific indication. The 2007 edition of the USP DI Drug Information lists infantile seizures (spasm) as an accepted indication for use of repository corticotropin injection. (3)

Possibly because of the side effects associated with repository corticotropin injection use as well as questions about long-term impact, other agents are being evaluated for this condition. In addition to vigabatrin, topiramate is also being studied. (4, 5)

Thus, given the data on the use of repository corticotropin injection, its long-standing use to treat infantile spasms, the uncertain efficacy of oral corticosteroids, and the clear lack of suitable alternatives, ACTH gel is considered one option for treatment of this condition.

Other than in infantile spasms, there is minimal published literature concerning use of repository corticotropin injection for conditions not considered steroid-responsive. For potential use in tobacco cessation, one article described an uncontrolled study of its use in 15 patients. (6) Thus, except for use in infantile spasm, use of repository corticotropin injection in conditions that are not responsive to corticosteroids is considered investigational.

Physician Specialty Society and Academic Medical Center Input

In response to the request for input from Physician Specialty Societies and Academic Medical Centers, input was received from one Academic Medical Center while this policy was under review. That Center agreed with the policy statements adopted in February 2008.

2009 Update

A search of the MEDLINE database was performed for the period February 2008 through July 2009.
The literature search identified: a meta-analysis, systematic review, three Cochrane Reviews, two professional society guidelines and one review article.

Gout

Underwood et al. (7) conducted a systematic review examining the effectiveness of treatments for acute gout. The authors concluded that repository corticotropin injection may be equally effective as corticosteroids at reducing symptoms in patients with acute gout. The evidence included one randomized controlled trial (n =31) of repository corticotropin injection versus a corticosteroid. The study did not include adverse events (harms). This evidence was given a low-quality rating by the authors.

Janssens et al. authored a Cochrane Review (8) that examined the efficacy and safety of systemic corticosteroids in the treatment of acute gout in comparison with placebo, NSAIDs (non steroidal anti-inflammatory drugs), colchicine, other active drugs, other therapies including repository corticotrophin injection, or no therapy. Clinically relevant differences between the studied systemic corticosteroids and the comparator drugs were not found; important safety problems attributable to the used corticosteroids were not reported. The quality of the three studies identified was graded as very low to moderate. Statistical pooling of results was not possible. The authors concluded that “There is inconclusive evidence for the efficacy and effectiveness of systemic corticosteroids in the treatment of acute gout.”

A review article by Schlesinger (9) discusses treatments for acute gout, emphasizing the use of repository corticotropin injection. The author notes that there are no formal guidelines for the treatment of acute gout and only a few randomized controlled trials (RCTs) have been conducted to evaluate the efficacy of the various treatments for acute gout. New research suggests that repository corticotropin injection acts peripherally by activation of the melanocortin type 3 receptor, and this could be responsible, at least in part, for its efficacy in acute gout. The author concludes that “Randomized, long term, prospective, placebo-controlled trials are needed to evaluate the therapeutic role of repository corticotropin injection versus NSAIDs (non steroidal anti-inflammatory drugs) and other treatment modalities, such as corticosteroids, in the treatment of acute gout.” Thus, some may not consider gout as a steroid responsive disease and may consider the use of repository corticotrophin.

Childhood Epilepsy

Gayatri et al. authored a Cochrane Review (10) to determine the efficacy of corticosteroids and repository corticotrophin injection in terms of seizure control, improvements in cognition, quality of life and tolerability compared to placebo or other antiepileptic drugs for the treatment of childhood epilepsy. All randomized controlled trials of administration of corticosteroids or repository corticotrophin injection to children (less than 16 years) with epilepsy were included. Outcomes included cessation of seizures, reduction in seizure frequency, improvement in cognition, quality of life and adverse effects. A single RCT was included that recruited five patients in a double-blind crossover trial. The authors concluded that “No evidence was found for the efficacy or safety of corticosteroids or repository corticotrophin injection in treating childhood epilepsies. Clinicians using steroids in childhood epilepsies, other than for epileptic spasms, should take this into account before using these agents.”

Infantile Spasms

Hancock et al. authored a Cochrane Review (11) to compare the effects of single drugs used to treat infantile spasms in terms of long-term psychomotor development, subsequent epilepsy, control of the spasms and adverse effects. Eleven RCTs (n =514) were included and tested eight different drugs. Overall, methodology of the studies was poor. No study assessed long-term psychomotor development or onset of other seizure types. The authors concluded that “We found no single treatment to be proven to be more efficacious in treating infantile spasms than any of the others (other than vigabatrin in the treatment of infantile spasms in tuberous sclerosis in one underpowered study). Few studies considered psychomotor development or subsequent seizure rates as outcomes and none had long-term follow-up. Further trials with larger numbers of participants, and longer follow-up are required.”

Summary

The available evidence for use of repository corticotropin injection for diagnostic testing of adrenocortical function and for treatment of infantile spasms (West’s syndrome) is sufficient to improve net health outcome. Therefore, the policy statements for these uses are considered as medically necessary.
The evidence is insufficient for the use of repository corticotropin injection as treatment of steroid-response conditions to improve net health outcome. Repository corticotropin injection is considered not medically necessary as treatment of steroid-response conditions, unless there are medical contraindications or intolerance to corticosteroids that are not also expected to occur with use of repository corticotropin injection.

The evidence is insufficient to support the use of repository corticotropin injection in conditions not responsive to corticosteroid therapy; tobacco cessation; acute gout; childhood epilepsy to improve net health outcome. The policy statement has been revised to the following: “Except as noted above, use of repository corticotropin injection is considered investigational for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation; acute gout; and childhood epilepsy.”

Guidelines and Position Statements

In May 2004, the American Academy of Neurology; Child Neurology Society released, Practice Parameter: Medical Treatment of Infantile Spasms: Report of the American Academy of Neurology and the Child Neurology Society. (2) The report states the following recommendations for adrenocorticotropin (ACTH): “ACTH is probably effective for the short-term treatment of infantile spasms and in the resolution of hypsarrythymia. There is insufficient evidence to recommend the optimum dosage and duration of treatment with ACTH for the treatment of infantile spasms.”

Medicare National Coverage
No national coverage determination.

References:

1. H.P. Acthar Gel product labeling. Accessible at www.acthar.com/Pdf/acthar_PI.pdf. Accessed August 2009.
2. 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(10):1668-81. (Also available online at http://www.neurology.org/cgi/content/full/62/10/1668 Accessed 01/30/08) Accessed August 2009.
3. Thompson Healthcare. Corticotropin (systemic) monograph. USP DI, Volume 1 Drug Information for the Health Care Professional. Greenwood Village, CO: Thompson Micromedex; 2007: 964-6.
4. Riikonen R. The latest on infantile spasms. Curr Opin Neurol 2005; 18(2):91-5.
5. Kwon YS, Jun YH, Hong YJ et al. Topiramate monotherapy in infantile spasm. Yonsei Med J 2006; 47(4):498-504.
6. McElhaney JL. Repository corticotrophin injection as an adjunct to smoking cessation during the initial nicotine withdrawal period: results from a family practice clinic. Clin Ther 1989; 11(6):846-53.
7. Underwood M. Gout. Clin Evid (Online) 2008; 2008, pii: 1120.
8. Janssens HJ, Lucassen PL, Van de Laar FA et al. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; (2):CD005521.
9. Schlesinger N. Overview of the management of acute gout and the role of adrenocorticotropic hormone. Drugs 2008; 68(4):407-15.
10. Gayatri NA, Ferrie CD, Cross H. Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms. Cochrane Database Syst Rev 2007; (1):CD005222.
11. Hancock E, Osborne JP, Milner P. Treatment of infantile spasms. Cochrane Database Syst Rev. 2002; (2):CD001770. Update in: Cochrane Database Syst Rev 2008; (4):CD001770.

Index

Policy History