| Coverage Policy Manual | |
| Policy #: | 2013048 |
| Category: | Pharmacy |
| Initiated: | December 2013 |
| Last Review: | August 2023 |
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| Repository Corticotropin Injection | |
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| Description: |
Repository corticotropin intramuscular or subcutaneous injection has primarily been used for treating infantile spasms (West syndrome). It has also been investigated for diagnostic testing of adrenocortical function and for treating a variety of other conditions.
Background
Repository corticotropin injection (H.P. Acthar® gel, Questcor Pharmaceuticals, Union City, CA) 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) in 1952, before there was a requirement that companies provide clinical evidence of efficacy. The product label states that Acthar gel is indicated for a number of conditions, listed below.
According to the prescribing information (i.e. product label), repository corticotropin injection may be used in the treatment of the following conditions:
Among the above indications, repository corticotropin injection is best known for the treatment of infantile spasms. This is a rare epileptic disorder of infancy (90% of cases are diagnosed in the first year of life). When infantile spasms are accompanied by neurodevelopmental regression and electroencephalogram (EEG) findings of hypsarrhythmia, the condition is known as West syndrome. Vigabatrin oral solution is another available treatment for infantile spasms.
A synthetic derivative of ACTH is commercially available outside of the United States (under the trade names Cortosyn and Synacthen) but it is not approved by the FDA for any of the conditions currently included in the H.P. Acthar gel FDA-approved label. In addition, a depot formulation of ACTH (Synacthen Depot) is available through a compassionate-use program through the specialty pharmacy Caligor Rx in New York. In June 2013, Questcor Pharmaceuticals announced that they acquired the rights to market Synacthen in the United States, once FDA approval is obtained.
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. Unlike previous versions of the H.P. Acthar product label, an updated label issued in 2010, did not mention the use of repository corticotropin injection for diagnostic testing of adrenocortical function.
Repository corticotropin injection has potential adverse effects similar to those that occur with steroid medication such as elevated blood pressure, decrease in bone density, new infections or activation of previous infection, and overproduction of cortisol, which can cause symptoms of Cushing’s syndrome.
Regulatory Status
H.P. Acthar gel (Questcor Pharmaceuticals) was approved by the FDA in 1952. The product label states that Acthar gel is indicated for 19 conditions, including infantile spasms. 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, uncontrolled hypertension, or sensitivity to proteins of porcine origin. Unlike previous versions of the product label, an updated label issued in 2010, did not include the use of repository corticotropin injection for diagnostic testing of adrenocortical function.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
Effective December 1, 2023, prior approval is required for repository corticotropin injection.
Effective August 23, 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Repository corticotropin injection as monotherapy for the treatment of infantile spasms (West syndrome) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for up to 4 weeks when ALL the following criteria are met (FDA H.P. Acthar Gel, 2010):
Dosing and Administration
Dosing per FDA Guidelines
Initial Dose: 75 U/square meters intramuscular twice daily for 2 weeks
After 2 weeks, dose should be tapered according to the following schedule: 20 U/square meters IM in the am for 3 days, then 15 U/square meters IM in the am for 3 days.
Repository corticotropin injection is available as 5 mL multi-dose vial containing 80 USP units per mL.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Not Medically Necessary or Investigational For Contracts Without Primary Coverage Criteria
The use of repository corticotropin injection for any indication or circumstance other than those described above including but not limited to corticosteroid-reponsive conditions, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes and is considered investigational.
For members with contracts without primary coverage criteria, repository corticotropin injection for any indication or circusmtance other than those described above including but limited to corticosteroid-reponsive conditions is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective August 2022 to August 22, 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Repository corticotropin injection as monotherapy for the treatment of infantile spasms (West syndrome) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for up to 4 weeks when ALL the following criteria are met (FDA H.P. Acthar Gel, 2010):
Dosing and Administration
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Not Medically Necessary or Investigational For Contracts Without Primary Coverage Criteria
The use of repository corticotropin injection as treatment of corticosteroid-responsive conditions does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes and is considered not medically necessary.
Repository corticotropin injection for use in diagnostic testing of adrenocortical function does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes and is considered not medically necessary.
Except as noted above, use of repository corticotropin injection for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation, acute gout, and childhood epilepsy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For individuals with contracts without primary coverage criteria, 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.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective August 2019 to July 2022
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Repository corticotropin injection as monotherapy for the treatment of infantile spasms (West syndrome) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for up to 4 weeks when ALL the following criteria are met (FDA H.P. Acthar Gel, 2010):
Dosing and Administration
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Not Medically Necessary or Investigational For Contracts Without Primary Coverage Criteria
The use of repository corticotropin injection as treatment of corticosteroid-responsive conditions does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Repository corticotropin injection for use in diagnostic testing of adrenocortical function does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Except as noted above, use of repository corticotropin injection for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation, acute gout, and childhood epilepsy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, 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. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
EFFECTIVE AUGUST 2016 to July 2019
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Repository corticotropin injection for the treatment of infantile spasms (West syndrome) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for up to 4 weeks when ALL of the following criteria are met:
Does Not Meet Primary Coverage Criteria Or Is Not Medically Necessary or Investigational For Contracts Without Primary Coverage Criteria
The use of repository corticotropin injection as treatment of corticosteroid-responsive conditions does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Repository corticotropin injection for use in diagnostic testing of adrenocortical function does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Except as noted above, use of repository corticotropin injection for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation, acute gout, and childhood epilepsy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, 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. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
EFFECTIVE PRIOR TO AUGUST 2016
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Repository corticotropin injection for the treatment of infantile spasms (West syndrome) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
Does Not Meet Primary Coverage Criteria Or Is Not Medically Necessary or Investigational For Contracts Without Primary Coverage Criteria
The use of repository corticotropin injection as treatment of corticosteroid-responsive conditions does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Repository corticotropin injection for use in diagnostic testing of adrenocortical function does not meet member benefit certificate primary coverage criteria of effectiveness and is considered not medically necessary.
Except as noted above, use of repository corticotropin injection for conditions that are not responsive to corticosteroid therapy including, but not limited to, use in tobacco cessation, acute gout, and childhood epilepsy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, 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. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Infantile spasms
In 2013, Hancock and colleagues published an updated Cochrane review on medication treatment of infantile spasms (Hancock, 2013). The authors identified 18 randomized controlled trials (RCTs) investigating a total of 12 different medications. The overall quality of studies was deemed to be poor i.e., fewer than half the study reported the method of randomization, and only 2 studies had more than 100 participants. A total of 5 studies compared treatment with adrenocorticotropic hormone (ACTH) to another medication. The review authors did not differentiate between synthetic and natural forms of ACTH. Two studies compared ACTH to vigabatrin (total sample sizes 9 and 42, respectively), 2 compared ACTH to prednisone (n=29 and 24, respectively), and 1 study with 52 participants compared ACTH to nitrazepam. A 6th study compared vigabatrin and ACTH in a subset of patients. Dosages and treatment regimens varied. The authors conducted several quantitative meta-analyses. A pooled analysis of 3 studies found that symptom resolution occurred in 30 of 45 patients (67%) responding to vigabatrin and 40 of 49 patients (82%) responding to ACTH. The difference between groups was statistically significant (odds ratio [OR]: 0.38, 95% confidence interval (CI): 0.15 to 0.99). The authors noted that the limited evidence from RCTs suggests that hormonal treatment (prednisolone, tetracosactide depot and ACTH) resolves infantile spasms faster than vigabatrin and resolves the condition in more children, but long-term developmental and epilepsy outcomes are unknown.
Section summary: There is some evidence from small, generally poor quality RCTs, that ACTH has greater short-term efficacy in resolving infantile spasms than vigabatrin.
Corticosteroid-responsive conditions
The product label for H.P. Acthar gel lists a number of corticosteroid-responsive conditions as indications for repository corticotropin injection, including rheumatoid arthritis, dermatomyositis, symptomatic sarcoidosis, nephrotic syndrome, multiple sclerosis (MS) exacerbations and serum sickness. Evidence that Acthar gel (i.e., ACTH) is a reasonable alternative to corticosteroid treatment requires controlled studies demonstrating superiority or non-inferiority of ACTH to corticosteroids as first-line treatment, or controlled studies showing comparable efficacy of ACTH with fewer adverse effects. Alternatively, for patients unable to tolerate corticosteroids, the most appropriate study design would be a controlled study comparing ACTH to placebo.
The only controlled studies were found for the treatment of MS (i.e., not for other indications). Several RCTs published in the 1960s and early 1970s compared ACTH to placebo for the treatment of acute exacerbations of MS. A study described in recent review articles as the most rigorous of these RCTs was published by Rose and colleagues (Rose, 1970; Rose, 1969). This was a multicenter, double-blind study that included 197 patients. Patients were randomized to receive intramuscular injections of ACTH gel or placebo during a 2-week hospitalization for acute exacerbations of MS. The study used Depo-ACTH and placebo, both prepared by the Upjohn Company. Review articles report that the study found that ACTH hastened improvement in symptoms but that the differences between the ACTH and placebo-treated patients was less marked as the dosage of ACTH was reduced during the second week of treatment (Berkovich, 2013).
Use of ACTH for treating MS exacerbations decreased in the 1980s as intravenous (IV) corticosteroid treatment became more common. Two RCTs published in the late 1980s compared ACTH to IV corticosteroids. A study by Milanese and colleagues with 30 patients found that dexamethasone was more effective than ACTH in shortening the length of the exacerbation (Milanese, 1989). Thompson and colleagues published a study that included 61 patients and compared ACTH and high-dose IV methylprednisolone (Thompson, 1989). The authors did not find a statistically significant difference in the efficacy of the 2 treatments. The study was powered to detect a 1-point difference between the 2 groups on Kurtzke’s function and disability scales. The scores before and after treatment were not reported.
There are also a limited number of small case series reporting on use of ACTH for other corticosteroid-responsive conditions. For example, in 2011, Bomback and colleagues published a retrospective case series in 21 patients with idiopathic, nondiabetic nephritic syndrome who were treated with ACTH gel. ACTH gel was used as a primary therapy in 3 patients; the other 18 patients had failed a mean of 2.3 immunosuppressive regimens before using ACTH gel (Bomback, 2011). An additional 5 patients were identified who were treated for less than 6 months and were taken off therapy for lack of response; these patients were not included in the analysis. Four of the 21 (19%) patients were in complete remission, defined as stable or improved renal function with final proteinuria falling to less than 500 mg/day. An additional 7 of 21 (33%) patients had a partial remission (at least a 50% reduction in proteinuria and final proteinuria 500 to 3,500 mg/day
Section summary: There is insufficient evidence that ACTH gel is at least as effective as IV corticosteroids for treatment of multiple sclerosis. One of 2 RCTs found that corticosteroids were more effective and the other found no significant difference in efficacy. There is a lack of evidence from controlled trials that ACTH is an effective treatment of other corticosteroid-responsive conditions.
Diagnostic testing of adrenocortical function
Diagnostic testing of adrenocortical function is typically done with synthetic ACTH. Studies have evaluated the value of synthetic ACTH for diagnosing adrenal insufficiency. For example, a 2008 meta-analysis identified 13 studies comparing low- and high-dose corticotropin tests for diagnosing adrenal insufficiency (Kazlauskaite, 2008). A comparable literature base was not identified for use of H.P. Acthar gel used in the diagnostic testing of adrenocortical function, and no studies were found that compared synthetic ACTH and Acthar gel for this purpose.
Non-corticosteroid-responsive conditions
Repository corticotropin injection has also been proposed for several off-label non-steroid-responsive conditions including tobacco cessation, acute gout, and childhood epilepsy. Controlled studies were identified only for treatment of acute gout. In 2008, Janssens and colleagues published a Cochrane review that examined the efficacy and safety of systemic corticosteroids in the treatment of acute gout in comparison with placebo, nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, other active drugs, other therapies including repository corticotropin injection, or no therapy (Janssens, 2008). Three head-to-head trials were identified; 1 of these compared systemic corticosteroids to oral indomethacine and intramuscular ACTH. The quality of the 3 studies identified was graded as very low to moderate. None of the studies found clinically relevant differences between the studied systemic corticosteroids and the comparator drugs and important safety problems attributable to the used corticosteroids were not reported. The authors concluded that “There is inconclusive evidence for the efficacy and effectiveness of systemic corticosteroids in the treatment of acute gout.”
Section summary: There is insufficient evidence from controlled trials that ACTH is a safe and effective treatment of non-corticosteroid-responsive treatments.
Ongoing clinical trials
A search of online site Clinicaltrials.gov database on November 12, 2013 identified 6 ongoing controlled trials evaluating Acthar gel. Four of the ongoing trials are placebo-controlled. Three studies are sponsored by Questcor Pharmaceuticals and, in the other 2 studies, Questcor Pharmacteuticals is a collaborator. The trials are as follows:
Acthar for treatment of proteinuria in diabetic nephropathy patients (NCT01601236): This is a pilot study randomizing patients to 1 of 3 doses of Acthar gel or equivalent volumes of placebo for 36 weeks with a 4-week dose taper. The primary study outcome is percent change in estimated glomerular filtration rate (eGFR) at week 36. The total sample size will be approximately 40 patients and the estimated completion date is June 2014.
Acthar for treatment of proteinuria in membranous nephropathy patients (NCT01386554): The study includes patients with treatment-resistant idiopathic membranous nephropathy. Patients will be randomized to an active treatment or placebo group and will be treated for 24 weeks. The primary outcome is the proportion of patients who have a complete or partial remission in proteinuria at week 28. The total sample size will be approximately 60 patients and the estimated completion date is June 2014.
Acthar for the treatment of systemic lupus erythematosus (SLE) in patients with a history of persistently active disease (NCT01753401): This study includes patients with steroid-dependent, persistently active SLE with arthritic and/or cutaneous involvement. Patients will be randomized to an active treatment or a placebo group. The primary outcome is the proportion of patients who are considered responders at week 4. The total sample size will be approximately 36 patients and the estimated completion date is December 2014.
ACTH in progressive forms of multiple sclerosis (MS) (NCT01950234): The study will compare Acthar gel given to MS patients using a pulsed regimen (i.e. injections on 3 consecutive days per month) and placebo. The primary outcome is the proportion of patients with a 20% worsening in the timed 25-foot walk test (T25FW) at 36 months. The study will include approximately 100 patients and the estimated completion dates is December 2017.
A Phase IV trial of neuroprotection with ACTH in acute optic neuritis (NCT01838174): The study includes patients with a diagnosis of clinically unilateral acute demyelinating optic neuritis and clinical signs and symptoms within the previous 14 days. Patients will be randomized to receive 15 days of daily injections of Acthar gel or 3 days of intravenous steroid injection followed by 11 days of oral steroid taper. The primary outcome is the average retinal nerve fiber layer (RNFL) thickness at 6 months. The study will include approximately 60 patients and the estimated completion dates is April 2015.
Summary
While questions still exist about the role of repository corticotropin injection in the treatment of infantile spasms, this has been accepted as a treatment option, and there is strong clinical support for this treatment. Thus, this use may be considered medically necessary.
There is insufficient evidence from controlled studies that repository corticotropin injection is at least as safe and effective as corticosteroid treatment for treating corticosteroid-responsive conditions, or is at least as safe and effective as synthetic ACTH for diagnostic testing of adrenocortical function. Because repository corticosteroid injection has not been found to be at least as beneficial as other approaches in the above situations, and because it is generally more costly than alternatives, it is considered not medically necessary for routine use.
There is a lack of evidence that repository corticotropin injection is at least as safe and effective as synthetic ACTH for diagnostic testing of adrenocortical function and thus, this is considered not medically necessary. The evidence is insufficient to support the use of repository corticotropin injection in conditions not responsive to corticosteroid therapy (such as tobacco cessation, acute gout, childhood epilepsy).
Practice Guidelines and Position Statements
In 2012, the American Academy of Neurology and the Practice Committee of the Child Neurology Society published an updated evidence-based guideline on treatment of infantile spasms (Go, 2012). The guideline included the following recommendations regarding use of ACTH:
In 2012, the American College of Rheumatology published guidelines on therapy and anti-inflammatory prophylaxis of acute gouty arthritis (Khanna, 2012). The guideline committee did not reach a consensus on use of ACTH for patients with acute gout who are able to take medications orally. For patients unable to take oral medications, the committee agreed that subcutaneous synthetic ACTH was a reasonable alternative to oral prednisone or prednisolone therapy.
In 2010, an industry-sponsored Infantile Spasms Working Group published a consensus report on diagnosis and treatment of infantile spasms (Pellock, 2010). Regarding treatment, the report concluded: “At this time, ACTH and VGB (vigabatrin) are the only drugs with proven efficacy to suppress clinical spasms and abolish the hyparrhythmic EEG in a randomized clinical trial setting (Mackay et al., 2004) and thus remain first-line treatment.”
2014 Update
A literature search conducted through November 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Since the Cochrane review, in 2014, an RCT was published that assigned children with previously untreated infantile spasms to treatment with 40-60IU synthetic ACTH every other day or 40-60 mg/day of oral prednisolone (Wanigasinghe, 2014). The study was conducted in Sri Lanka and uses a form of ACTH that is not FDAapproved for this indication. The primary outcome, assessed in a blinded fashion after a 14-day treatment period, was change in a hypsarrhythmia severity scale (possible range, score of 0 to 16). Hypsarrhythmia is an abnormal interictal pattern seen on an EEG and can be considered an intermediate outcome; clinical outcomes such as symptom resolution were not assessed. Ninety-two children were randomized and follow-up data were available on 80 (82%) of them. Mean improvement in the hypersarrhythmia score was 7.95 (SD: 2.76) in the prednisolone arm and 6.00 (SD: 2.61) in the ACTH arm. The between-group difference was significantly different, p<0.01, favoring treatment with prednisolone. Rates of adverse effects were similar in the 2 groups. This study suggests that prednisolone may at least as effective as synthetic ACTH for treatment of infantile spams. However, the study has methodologic limitations including a dropout rate of over 20%, lack of intention to treat analysis, short-term follow-up only, and use of intermediate outcomes.
There is some evidence from small, generally poor quality RCTs, that natural and synthetic ACTH has greater short-term efficacy in resolving infantile spasms than vigabatrin. A 2014 RCT suggests that prednisolone may be at least as effective in the short-term as synthetic ACTH in the treatment of infantile spasms.
2015 Update
A literature search conducted through November 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
A study done by Lal and colleagues looked at the pharmacodynamics and tolerability of ACTH in comparison to IV methylprednisolone (IVMP) (Lal, 2015). This was a multiple-dose, randomized open-label crossover study which enrolled 18 healthy patients to evaluate the total cortisol-equivalent exposure, effects on circulating immune cells, and tolerability of ACTH and IVMP. The authors concluded that ACTH may cause less systemic immunosuppression relative to equivalent doses of IVMP, which may be of benefit in autoimmune disorders, such as multiple sclerosis. This is a small study done in healthy patients, which offered no clinical outcomes. Further studies are needed to evaluate this data.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below:
Ongoing:
NCT02290444 Effects of Acthar on Recovery From Cognitive Relapses in MS; planned enrollment 60d; completion date August 2016.
NCT02132195 Industry-sponsored or cosponsored trial. Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome; planned enrollment 60; completion date October 2016.
NCT02315872 Industry-sponsored or cosponsored trial. ACTH for Fatigue in Multiple Sclerosis Patients; planned enrollment 90; completion date December 2016.
The evidence for repository corticotropin injection in patients with Infantile Spasms includes RCTs and a Cochrane systematic review. Relevant outcomes included symptoms and change in disease status. The overall quality of the studies is deemed poor with fewer than half of the studies reporting method of randomization, relatively small numbers of patients, lack of differentiation between synthetic and natural forms of ACTH, and various dosage and treatment regimens utilized in the studies. Most studies were done in comparison with either vigabatrin or prednisolone. Some of the RCTs, and the Cochrane review, report improved response with repository corticotropin, but other RCTs do not. The most recent RCT published in 2014 reported that repository corticotropin was less effective than prednisolone, although clinical outcomes were not reported. The evidence is insufficient to determine the effects of the technology on health outcomes.
Based on the results of clinical input, there is strong clinical support for the use of repository corticotropin injection for patients with Infantile Spasms and this is considered standard of care. Therefore, treatment of infantile spasms may be considered medically necessary.
The evidence for repository corticotropin injection for patients with corticosteroid-responsive conditions (including rheumatoid arthritis, dermatomyositis, sarcoidosis, nephrotic syndrome, multiple sclerosis and serum sickness) includes RCTs and small cases series. Relevant outcomes include symptoms and change in disease status. Overall, more recent studies done in MS have demonstrated that IV corticosteroids are at least as effective, or more effective, than repository corticotropin. Studies done in nephrotic syndrome have been mainly small, retrospective case studies, although there are ongoing studies being done. The evidence is insufficient to determine the effects of the technology on health outcomes.
The evidence for repository corticotropin injection for patients with non-corticosteroid-responsive conditions (such as for tobacco cessation, childhood epilepsy and acute gout) includes three head-to-head trials identified for use in gout. Relevant outcomes include symptoms. The quality of these studies was deemed poor as there were no direct placebo-controlled trials and there were no clinically relevant differences found between drugs studied. The evidence is insufficient to determine the effects of the technology on health outcomes.
The evidence for repository corticotropin injection for diagnosing adrenal cortical function includes no studies that report on diagnostic accuracy compared to ACTH. Relevant outcomes include test accuracy, test validity, and other test performance measures. The lack of published evidence precludes conclusions on the validity of using repository corticotropin as a diagnostic test for adrenal function. The evidence is insufficient to determine the effects of the technology on health outcomes.
2017 Update
A literature search conducted through July 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Findings from a prospective national database of children with infantile spasms were published by Knupp and colleagues (Knupp, 2016). A total of 230 infants were included in the database and 94 responded to initial treatment for infantile spasms. Response rate by type of treatment was 55 (55%) for ACTH, 21 (39%) for oral corticosteroids, 17 (36%) for vigabatrin, and 2 (9%) for “other” (p<0.001). The type of ACTH, natural or synthetic, was not specified. The study was not randomized and groups may have differed on characteristics that affect outcomes. Some significant differences between groups were identified, for example length of time from diagnosis to the start of treatment and history of prior seizures. In logistic regression models controlling for some potential confounding factor, children on ACTH remained more likely to respond to treatment than other children. However, there may be residual confounding on unmeasured characteristics.
2018 Update
A literature search conducted using the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below:
Ongoing:
NCT02290444 - Effects of Acthar on Recovery From Cognitive Relapses in MS; 60 enrolled participants; Completion date December 2017.
NCT02132195 - Industry-sponsored or cosponsored trial. Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome; 60 enrolled participants; Completion date October 2018.
NCT02315872 - Industry-sponsored or cosponsored trial. ACTH for Fatigue in Multiple Sclerosis Patients; 8 enrolled participants. Completion date December 2019
2019 Update
Gillis et al (2017) published a small case series of 8 adults with confirmed rheumatoid arthritis and American College of Radiology functional status between 1 and 3. Patients were refractory to prior therapies with at least 3 different modes of action. Repository corticotropin injection was administered for 12 weeks, with follow-up visits at weeks 14 and 16 (after cessation of repository corticotropin injection). Both physician and patient visual analog scale assessments of swollen and tender joints improved from baseline to 12 weeks: physician visual analog scale scores significantly decreased from median of 8.4 (range, 3.8-9.9) to 2.5 (range, 0.30-6.5; p<0.001); patient visual analog scale scores decreased from median of 28.5 (range, 8-97) to 17 (range, 0-40; p=0.022). The 28-item Disease Activity Score for rheumatoid arthritis was also used as an outcome measure. As an open-label, unblinded study, there was potential for sampling bias, and patients were permitted to continue a variety of concomitant medication during repository corticotropin injection treatment.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement.
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Berkovich R.(2013) Treatment of acute relapses in multiple sclerosis. Neurotherapeutics 2013; 10(1):97-105. Bomback AS, Tumlin JA, Baranski J et al.(2011) Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther 2011; 5:147-53. Gillis T, Crane M, Hinkle C, et al.(2017) Repository corticotropin injection as adjunctive therapy in patients with rheumatoid arthritis who have failed previous therapies with at least three different modes of action. Open Access Rheumatol. Aug 2017;9:131-138. PMID 28790870 Go CY, Mackay MT, Weiss SK et al.(2012) 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(24):1974-80. H.P. Actar Gel Product Label. Available online at: http://www.acthar.com/pdf/Acthar-PI.pdf. Last accessed November, 2013. H.P. Acthar Gel FDA Label. 2010. Available online at https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022432s000lbl.pdf. Last accessed September 9, 2021. Hancock EC, Osborne JP, Edwards SW.(2013) Treatment of infantile spasms. Cochrane Database Syst Rev 2013; 6:CD001770. Janssens HJ, Lucassen PL, Van de Laar FA et al.(2008) Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; (2):CD005521. Kazlauskaite R, Evans AT, Villabona CV et al.(2008) Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008; 93(11):4245-53. Khanna D, Khanna PP, Fitzgerald JD et al.(2012) 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012; 64(10):1447-61. Knupp KG, Coryell J, Nickels KC, et al.(2016) Response to treatment in a prospective national infantile spasms cohort. Ann Neurol. Mar 2016;79(3):475-484. PMID 26704170 Lal R, Bell S, Challenger R, et al.(2015) Pharmacodynamics and tolerability of repository corticotropin injection in healthy human subjects: A comparison with intravenous methylprednisolone. J Clin Pharmacol. Jun 26 2015. PMID 26120075 Milanese C, La Mantia L, Salmaggi A et al.(1989) 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. Pellock JM, Hrachovy R, Shinnar S et al.(2010) Infantile spasms: a U.S. consensus report. Epilepsia 2010; 51(10):2175-89. Rose AS, Kuzma JW, Kurtzke JF et al.(1969) Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo in acute exacerbation. Trans Am Neurol Assoc 1969; 94:126-33. Rose AS, Kuzma JW, Kurtzke JF et al.(1970) Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology 1970; 20(5):1-59. Thompson AJ, Kennard C, Swash M et al.(1989) Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology 1989; 39(7):969-71. Tibussek D, Klepper J, Korinthenberg R, et al.(2016) Treatment of Infantile Spasms: Report of the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society for Neuropediatrics. Neuropediatrics. Jun 2016;47(3):139-150. PMID 269 Wanigasinghe J, Arambepola C, Sri Ranganathan S, et al.(2014) The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: a randomized, single-blind, parallel clinical trial. Pediatr Neurol. Jul 2014;51(1):24-30. PMID 24938136 |
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