Repository corticotropin injection is a preparation of the natural form of adrenocorticotropic hormone (ACTH). The injection is used to treat corticosteroid-responsive conditions and as a diagnostic tool to test adrenal function.
For individuals who have infantile spasms who receive repository corticotropin injection, the evidence includes systematic reviews/meta-analyses and a prospective study. Relevant outcomes are symptoms and change in disease status. A 2013 systematic review judged the overall quality of all included studies involving various medications for infantile spasms to be poor, with fewer than half reporting method of randomization and most assessing relatively few patients. There was heterogeneity across studies and either vigabatrin or prednisolone was used as comparators; however, the authors concluded that limited evidence from randomized controlled trials (RCTs) suggested that adrenocorticotropic hormone (ACTH) and prednisolone resolved infantile spasms more rapidly than vigabatrin. More recent meta-analyses also concluded that ACTH treatment was non-inferior to corticosteroid treatment with a similar adverse event profile and may be considered a safe and effective alternative treatment. A 2021 systematic review including 6 trials indirectly compared natural ACTH with synthetic ACTH therapies. Based on the limited evidence included, investigators suggested that repository corticotropin injection may be a better treatment option over synthetic ACTH therapies for improving cessation of spasms and other relevant symptoms. Multivariate analysis of a prospective cohort study found that children with infantile spasms who were treated with ACTH were more likely to respond than other children. However, the analysis might have been subject to residual confounding on unmeasured characteristics; further, the study did not differentiate between synthetic and natural ACTH. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have corticosteroid-responsive conditions (eg, rheumatoid arthritis, dermatomyositis, sarcoidosis, nephrotic syndrome, multiple sclerosis [MS], serum sickness, systemic lupus erythematosus [SLE]) who receive repository corticotropin injection, the evidence includes RCTs and observational studies. Relevant outcomes are symptoms and change in disease status. One placebo-controlled trial supports the efficacy of repository corticotropin injection in patients with rheumatoid arthritis and an inadequate response to corticosteroids and disease-modifying therapies. Overall, more recent studies evaluating MS have demonstrated that IV corticosteroids are at least as effective, or more effective, than repository corticotropin injection. A recent RCT in patients with SLE found no difference in SLE Responder Index-4 responders in the repository corticotropin group compared to placebo. Most studies assessing nephrotic syndrome have been small retrospective case studies and the 1 RCT identified stopped early due to lack of efficacy of ACTH.. Ongoing studies are being conducted. A randomized trial in patients with pulmonary sarcoidosis was insufficiently powered due to low enrollment.In patients with cutaneous dermatomyositis, a small (n=19) prospective study found improved disease severity scores after 6 months of treatment with repository corticotropin injection. In patients with sarcoidosis, a retrospective study using an administrative claims database demonstrated corticosteroid-sparing effects following therapy with repository corticotropin injections. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have conditions not generally known to be responsive to corticosteroids (non-corticosteroid-responsive) such as tobacco cessation, childhood epilepsy, and acute gout who receive repository corticotropin injection, the evidence includes 3 head-to-head trials identified for use in gout. Relevant outcomes are symptoms and change in disease status. The quality of these studies was deemed very low to moderate because there were no direct placebo-controlled trials and no clinically relevant differences were detected between drugs studied. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who need diagnostic testing of adrenal function who receive repository corticotropin injection, the evidence does not include studies that compare the diagnostic accuracy of repository corticotropin injection with ACTH. Relevant outcomes are test validity and other test performance measures. The lack of published evidence precludes conclusions on the validity of using repository corticotropin injection as a diagnostic test for adrenal function. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
Repository corticotropin injection may be considered medically necessary for the treatment of infantile spasms (West syndrome).
Use of repository corticotropin injection is considered investigational as a treatment of corticosteroid-responsive conditions (see Policy Guidelines section).
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.
Repository corticotropin injection is considered investigational for use in diagnostic testing of adrenocortical function.
| CPT | 96372 | Therapeutic, prophylactic or diagnostic injection (specify substance or drug); subcutaneous or intramuscular |
| HCPCS | J0800 | Injection, corticotropin, up to 40 units |
| J0801 | Injection, corticotropin (acthar gel), up to 40 units |
| ICD-10-CM | G40.821-G40.824 | Epileptic spasms code range (includes infantile spasms) |
Some individuals may have medical contraindications or intolerance to corticosteroids that are not expected to occur with use of repository corticotropin injection, and who therefore may benefit from repository corticotropin injections. This situation is not common.
Product information provides the following on dosage of H.P. Acthar® Gel for treatment of infantile spasms:
In the treatment of infantile spasms, the recommended dose is 150 U/m2 divided into twice daily intramuscular injections of 75 U/m2. After 2 weeks of treatment, dosing should be gradually tapered and discontinued over a 2-week period.
In the treatment of other disorders and diseases, dosing will need to be individualized, depending on the disease under treatment and the medical condition of the individual (it may be necessary to taper the dose).
H.P. Acthar Gel is used for intramuscular or subcutaneous injection and should never be used intravenously.
Repository corticotropin injection (H.P. Acthar Gel) is a purified, sterile preparation of the natural form of adrenocorticotropic hormone (ACTH) in gelatin to provide a prolonged release after intramuscular or subcutaneous injection. ACTH is produced and secreted by the pituitary gland; H.P. Acthar Gel uses ACTH obtained from porcine pituitaries. ACTH works by stimulating the adrenal cortex to produce cortisol, corticosterone, and a number of other hormones.
H.P. Acthar Gel was approved by the U.S.Food and Drug Administration (FDA) before the requirement that companies provide evidence of clinical efficacy. Table 1 summarizes the current prescribing indications and usage for Acthar Gel.1, In 2006, a review of an efficacy supplement for the infantile spasms indication was initiated. The sponsor was requested to provide a dossier of safety and efficacy data from preexisting clinical trials and archival literature. In 2010, the FDA finalized this review and determined there was sufficient scientific and clinical evidence to support its use for the infantile spasms indication.2,
| Indication | Populations or Conditions |
| Infantile spasms | Monotherapy for infants and children <2 years of age |
| Multiple sclerosisa | Acute exacerbations of multiple sclerosis in adults |
| Rheumatic disorders | Adjunctive therapy for short-term administration for acute episodes or exacerbations of psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis), and ankylosing spondylitis |
| Collagen diseases | During an exacerbation or as maintenance therapy in select cases of systemic lupus erythematosus and systemic dermatomyositis (polymyositis) |
| Dermatologic diseases | Severe erythema multiforme and Stevens-Johnson syndrome |
| Allergic states | Serum sickness |
| Ophthalmic diseasesb | Severe acute and chronic allergic and inflammatory processes |
| Respiratory diseases | Symptomatic sarcoidosis |
| Edematous statec | To induce a diuresis or a remission of proteinuria in nephrotic syndrome |
a Controlled trials have shown H.P. Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.
b Keratitis; iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis; anterior segment inflammation.
c Without uremia of the idiopathic type or due to lupus erythematosus.
Diagnostic testing of adrenocortical function, known as the ACTH test, is typically done with synthetic ACTH. Synthetic ACTH products have been approved by the FDA for this purpose.
Contraindications for the 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, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, suspected congenital infection in infants, concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar Gel, or sensitivity to proteins of porcine origin.
Repository corticotropin injection has potential adverse events similar to those that occur with other steroid medications such as elevated blood pressure, a decrease in bone density, new infections (or activation of previous infection), and overproduction of cortisol, which can cause symptoms of Cushing syndrome.
In 1952, H.P. Acthar Gel (Questcor Pharmaceuticals/Mallinckrodt Pharmaceuticals) was approved by the FDA. The original product label included at least 19 separate conditions, including infantile spasms. A 1979 efficacy supplement added the treatment of acute exacerbation of multiple sclerosis. At one time, this product was indicated as an injection for diagnostic testing of adrenocortical function. In 2010, this indication was removed with an update to the product label.
