BlueCross BlueShield of Tennessee Medical Policy Manual

Corticotropin Therapy (HP Acthar®)

NDC CODE(S)

63004-8710-XX HP Acthar 80 UNIT/ML Gel or Solution (QUESTCOR)

DESCRIPTION

Corticotropin is a highly purified sterile preparation of adrenocorticotropic hormone (ACTH).  It is currently only commercially available in gelatin to provide a prolonged release in tissues after subcutaneous or intramuscular injection.  ACTH stimulates the adrenal cortex to produce multiple hormones, including cortisol, corticosterone and aldosterone.

POLICY

·         Corticotropin therapy for the treatment of infantile spasms (West syndrome) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

·         Corticotropin therapy for diagnostic testing of adrenocortical function is considered not medically necessary.

·         Corticotropin therapy for the treatment of other conditions/diseases is considered investigational.

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Infantile spasms (West Syndrome)

·         Patient is under 2 years of age; AND

·         Clinical documentation indicating patient has a diagnosis of infantile spasms (West Syndrome); AND

·         Must be used as monotherapy; AND

·         Documentation that patient does not have a suspected congenital infection

 

Use of repository corticotropin injection for indications including but not limited to those additionally listed in the product labeling are not supported by substantial clinical evidence.

Repository Corticotropin Injection was originally approved by the U.S. Food and Drug Administration (FDA) in 1952 for a variety of disorders and diseases that at the time were thought to benefit from steroid mediated immunosuppression. The initial approval of H.P. ACTH gel occurred prior to the Kefauver-Harris amendment to the Federal Food, Drug and Cosmetic Act of 1962, which introduced the requirement of “substantial evidence” of two adequate and well controlled trials. At the time of the original approval drug manufacturers only had to show the drug was safe for use in humans. The original data included case reports from a few physicians describing patients with conditions originally treated with Acthar powder that were transferred to treatment with Acthar Gel and gave dosing guidance for treatment of these individual conditions. These data would be grossly inadequate to support approval of a new drug or new indications by the Agency under current standards requiring evidence from adequate and well-controlled clinical trials. A Drug Efficacy Study Implementation (DESI) review of corticotrophin injection was initiated in 1971 and finalized in 1977.3

RENEWAL CRITERIA

·         Patient continues to meet indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in the Initial Approval Criteria; AND

·         Disease response with treatment as indicated by resolution of symptoms and/or normalization of laboratory tests; AND

·         Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: severe infections, severe electrolyte imbalances, gastric bleeding or ulcer, hypertension, hypokalemia, severe depression, frank psychotic manifestations, posterior subcapsular cataracts, glaucoma, etc.

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Infantile Spasms

Administer 75 units/m² intramuscularly given twice daily for 2 weeks, then taper the dose over a 2 week period (e.g., 30 units/m2 in the morning for 3 days; 15 units/m2 in the morning for 3 days; 10 units/m2 in the morning for 3 days; and 10 units/m2 every other morning for 6 days).

LENGTH OF AUTHORIZATION

Coverage will be provided for 1 month and may be renewed.

DOSING LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

·         35 billable units every 28 days

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     H.P. Acthar Gel [package insert]. Bedminster, NJ; Mallinckrodt Pharmaceuticals Inc; February 2021. Accessed February 2021.

2.     Center for Drug Evaluation and Research. APPLICATION NUMBER: 022432Orig1s000. Approval Package. U. S. Food and Drug Administration. Washington, DC.

3.     Center for Drug Evaluation and Research. APPLICATION NUMBER: 022432Orig1s000. Other Review(s). U. S. Food and Drug Administration. Washington, DC.

4.     Go, C.Y., Mackay, M.T., Weiss, S.K. et al. Evidence-based guideline update: Medical treatment of infantile spasms: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2012;78;1974-1980.

5.     Hussain SA, Shinnar S, Kwong G, et al. Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone. Epilepsia. 2014 Jan;55(1):103-7. doi: 10.1111/epi.12460. Epub 2013 Nov 8.

6.     Hrachovy RA, Frost JD, Glaze DG et al. High-dose, long-duration versus low-dose, short duration corticotropin therapy for infantile spasms. J Pediatr 1994;124:803-806.

7.     Kivity S, Lerman P, Ariel R, et al. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia. 2004 Mar;45(3):255-62.

8.     Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010 Oct;51(10):2175-89.

9.     M. T. Mackay, S. K. Weiss, T. Adams-Webber, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology 2004;62;1668-81.

10.  Hussain S, et al "Treatment of infantile spasms with very high dose prednisolone before high dose ACTH" AES 2012; Abstract 1.247.

11.  Baram TZ, Mitchell WG, Tournay A et al. High-dose corticotropin (ACTH) versus prednisone for infantile spasm: A prospective, randomized, blinded study. Pediatrics. 1996 Mar; 97(3): 375–379.

12.  Hrachovy RA, Frost JD, Kellaway P, et al. Double-blind study of ACTH vs. prednisone therapy in infantile spasms. J Pediatr 1983 Oct; Volume 103: pp 641-5.

13.  Snead OC, Benton WJ, Myers JG. ACTH and prednisone in childhood seizure disorders. Neurology 1983; Volume 33: pp 966.

14.  Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study. Epilepsia Dec1997; 38:1270-4.

15.  Cossette P, Riviello J, Carmant L. ACTH versus vigabatrin therapy in infantile spasms: A retrospective study. Neurology 12 May 1999; Volume 52: 1691-1694.

16.  Grasntrom ML, Gaily E, Liukkonen E, et al. Treatment of infantile spasms: results of a population-based study with vigabatrin as the first drug for spasms. Epilepsia 1999 July; Volume 40: pp 950-7.

17.  Appleton RE, Peters AC, Mumford JP, et al. Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia 1999 Nov; Volume 40; pp 1627-33.

18.  Gettig J, Cummings JP, Matuszewski K. H.P. Acthar Gel and Cosyntropin Review: Clinical and Financial Implications. P T. 2009 May;34(5):250-257.

19.  Philbin M, Niewoehner J, Wan G. Clinical and Economic Evaluation of Repository Corticotropin Injection: A Narrative Literature Review of Treatment Efficacy and Healthcare Resource Utilization for Seven Key Indications. Adv Ther. 2017; 34(8): 1775–1790.

20.  Thompson AJ, Kennard C, Swash M, et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989 Jul;39(7):969-71.

21.  Abbruzzese G, Gandolfo C, Loeb C. “Bolus” methylprednisolone versus ACTH in the treatment of multiple sclerosis. The Italian Journal of Neurological Sciences, 1983, Volume 4, Number 2, Page 169.

22.  National Medical Advisory Board of the National Multiple Sclerosis Society. Expert Opinion Paper: Recommendations Regarding Corticosteroids in the Management of Multiple Sclerosis. US Neurology, 2008;4(1):22-24.

23.  National Clinical Guideline Centre. Multiple sclerosis: management of multiple sclerosis in primary and secondary care. London (UK): National Institute for Health and Care Excellence (NICE); 2014 Oct. 36 p. (Clinical guideline; no. 186).

24.  Citterio A, La Mantia L, Ciucci G, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.:CD001331.

25.  Simsarian JP, Saunders C, Smith DM. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: A prospective, randomized, open-label pilot trial. Drug Des Devel Ther. 2011;5:381-389.

26.  Cortese I, Chaudhry V, So Y, Cantor F, Cornblath D, Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011:76(3):294.

27.  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(1):10-4.

28.  Filippini G, Brusaferri F, Sibley WA, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000;(4):CD001331.

29.  Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2:139–274.

30.  Wang C, Travers C, McCracken C, et al. Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome. CJASN December 2018, 13 (12) 1859-1865.

31.  Lombel RM, Hodson EM, Gipson DS. Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatr Nephrol 2013;28:409-14.

32.  Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011;5:147-153.

33.  Madan A, Mijovic-Das S, Stankovic A, et al. Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective case series. BMC Nephrol. 2016; 17:37.

34.  Bomback AS, Canetta PA, Beck LH Jr, et al. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012; 36(1):58-67.

35.  Chen Y, Schieppati A, Cai G, et al. Immunosuppression for membranous nephropathy: a systematic review and meta-analysis of 36 clinical trials. Clin J Am Soc Nephrol. 2013; 8(5):787-796.

36.  Watson MJ. Membranous glomerulopathy and treatment with Acthar® : a case study. Int J Nephrol Renovasc Dis. 2013; 6:229-232.

37.  Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: A pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1. J Diabetes Res. 2013;2013:489869.

38.  Hogan J, Bomback AS, Mehta K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013; 8(12): 2072.

39.  Hladunewich MA, Cattran D, Beck LH, et al. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant. 2014 Aug;29(8):1570-7.

40.  Hogan J, Radhakrishnan J. The treatment of minimal change disease in adults. J Am Soc Nephrol 2013;24:702-11.

41.  Bertsias GK, Tektonidu M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and pediatric lupus nephritis. Ann Rheum Dis 2012;71:1771-82.

42.  Fiechtner J, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: A single-site, open-label trial. Lupus. 2014;23(9):905-912.

43.  Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: A retrospective case series. Drug Des Devel Ther. 2012;6:133-139.

44.  Baughman RP, Sweiss N, Keijsers R, et al. Repository corticotropin for chronic pulmonary sarcoidosis. Lung. 2017; 195(3):313-322.

45.  Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65:137-74.

46.  Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol 2012;51:889-902.

47.  Lexicomp Online. (2020, March). AHFS DI. Corticotropin (pituitary). Retrieved April 22, 2020 from Lexicomp Online with AHFS.

48.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2019, December). Corticotropin. Retrieved April 22, 2020 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE: 9/14/2008

MOST RECENT REVIEW DATE:    8/31/2021

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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