Acthar Gel Research Articles

Clinical assessment of the potential use of a novel single-dose prefilled injection device for the administration of Acthar Gel in children: a narrative review.

Acthar® Gel (repository corticotropin injection; Mallinckrodt Pharmaceuticals, NJ, USA) is indicated for the treatment of myriad inflammatory disorders and is currently administered manually via a vial and syringe. The administration of Acthar via a single-dose prefilled injector (SelfJect™) is intended to simplify its subcutaneous (SC) delivery. The purpose of this review was to determine whether SelfJect is suitable for use in pediatric patients through a literature assessment of various factors, including skin depth, needle length and gauge, dosage, force required for injection, and potential harms. Infants and young children, who commonly have skin-to-muscle distances less than the minimum depth of SelfJect administration, may have risk of unintentional intramuscular (IM) injection; however, an inadvertent IM injection poses no additional risk to children because of the bioequivalence between SC and IM administration of Acthar. The needle gauge of SelfJect is acceptable for pediatric patients and aligns with the Centers for Disease Control and Prevention recommendations for SC injections. The dosage delivered by SelfJect is only appropriate for children over 2years of age. Although adolescents would likely be able to achieve the minimum force required to remove the protective cap and deliver a full dose of Acthar with SelfJect, an adult (18years of age and older) should administer SelfJect to pediatric patients. In addition to the commonly reported postmarketing adverse events (AEs) from Acthar administration (e.g., asthenic conditions, fluid retention, insomnia, headache and increased blood glucose), injection site-related AEs common to injection devices may occur with SelfJect use. The risk of needlestick injury from SelfJect is mitigated by a needle guard. In summary, this review of injection device considerations demonstrates that SelfJect is appropriate for use in the pediatric population.

Formative and validation human factors studies of a new disposable prefilled injection device for subcutaneous delivery of acthar gel (repository corticotropin injection)

ABSTRACT Background The administration of repository corticotropin injection (Acthar Gel) via a single-dose prefilled injector (SelfJect) is intended to provide a simple, ergonomic alternative to traditional injection. Iterative human factors (HF) studies were conducted to identify potential use deviations and ensure appropriate device use. Research design and methods This article presents seven formative studies, a validation study (with prior pilot validation studies), and a supplemental validation study with participants including lay users, patients, caregivers, and healthcare providers. Participant interactions with SelfJect and the user interface were assessed. Use deviations, user preferences, and participants’ ability to successfully complete tasks were evaluated to generate modifications to the device and user interface. Results In the validation study, 91% of participants successfully administered their first injection. Use errors were rare with simulated-use (6.9%) and knowledge-based (1.6%) testing. Use deviations were commonly attributed to experimental artifact or information oversight, and device warming had the most use errors (49% of participants), even with extensive testing and adjustments to the user interface. Conclusions SelfJect was able to be used in a safe and effective manner by the intended users. Iterative HF studies informed the mitigation of use-related risks to reduce the occurrence of use deviations during simulated use.

Acthar Gel in African Americans versus Non-African Americans with Symptomatic Sarcoidosis: Physician Assessment of Patient Medical Records.

Sarcoidosis is common among African Americans in the United States. Acthar® Gel is a viable option for the treatment of advanced symptomatic sarcoidosis. This study examined patient characteristics, Acthar Gel utilization, co-medication use, and treatment response based on physicians' assessments among African Americans versus non-African Americans with advanced symptomatic sarcoidosis. Data from the medical charts of patients were used. During data collection, patients had either completed ≥1 course or received treatment with Acthar Gel for ≥6 months. This study comprised 168 African Americans and 104 non-African Americans. On average, the time since the first diagnosis of sarcoidosis was slightly longer among African Americans than non-African Americans (5.2 versus 4.3 years). Skin, heart, eyes, and joints were the most common extrapulmonary sites involved among both race groups. Shortness of breath, fatigue, bone and joint pain, and wheezing/coughing were the most frequent symptoms among both race groups. A higher proportion of African Americans versus non-African Americans were first-time Acthar Gel users and had not completed treatment during data collection. Patients in both race groups with higher starting doses of Acthar Gel therapy had a shorter treatment duration and vice-versa. A significantly lower proportion of patients among both race groups were on any co-medication after Acthar Gel initiation (p<0.0001). Further, a higher proportion of African Americans versus non-African Americans had a reduction in any co-medication use after Acthar Gel initiation. The mean daily dose of prednisone decreased among African Americans (18.5 to 10.1 mg) and non-African Americans (17.6 to 10.0 mg) after Acthar Gel initiation. Improvement in patient health status and overall symptoms was similar for both race groups. Findings suggest that Acthar Gel improves health outcomes for patients with sarcoidosis, which could help to alleviate health disparities among African Americans, who are disproportionately affected by this disease.

Response to Acthar Gel in sarcoidosis uveitis: A prospective open label study

PurposeTo investigate the response to Acthar Gel® in patients with moderate to severe sarcoidosis uveitis. MethodsThis is a prospective open-label study that enrolled patients with moderate to severe sarcoidosis uveitis to receive 80 units daily of Acthar Gel for ten days followed by maintenance treatment with 80 units twice weekly. The primary outcome was the proportion of patients meeting at least one of the following variables 1) improved visual acuity, 2) resolution of intraocular inflammation, 3) ability to taper ocular or oral steroids by at least 50% or 4) reduction of cystoid macular edema, with no worsening of any single measure and no need for additional sarcoidosis therapies at 24 weeks. ResultsA total of nine patients were enrolled in the study. Four patients completed the full 24-week course of Acthar Gel, and three of these met the primary endpoint. Among the five patients who did not complete the 24-week course of treatment, four discontinued the treatment due to worsening ocular inflammation. One patient discontinued treatment due to severe adverse effects. The most common adverse effects were fluid retention (77%), insomnia (44%), hypertension (44%) and hyperglycemia (44%). ConclusionsWe observed a clinical response to Acthar Gel in some patients with moderate to severe sarcoidosis uveitis, but a substantial proportion either failed to respond or did not tolerate the therapy. These observations may serve as preliminary data for controlled trials of Acthar Gel, but they do not support its role prior to failure of other agents.

Cost-Effectiveness of Acthar Gel versus Standard of Care for the Treatment of Advanced Symptomatic Sarcoidosis.

Sarcoidosis is a multisystem, inflammatory, systemic granulomatous disease with unknown etiology. Despite the current standard of care (SoC), there is an unmet need for the treatment of advanced symptomatic sarcoidosis. This study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC in patients with advanced symptomatic sarcoidosis from the United States (US) payer and societal perspectives over 2 and 3 years. A probabilistic cohort-level state-transition approach was used for this cost-effectiveness analysis. Patients were monitored at the end of a 3-month cycle for the attainment of partial or complete response. Patients in the partial, complete, or no-response state were allowed to transition in each of these states at each 3-month cycle. Following the attainment of response, patients could have a durable response or relapse to a no-response state. Patients in a no-response state received treatment and could transition into a response or no-response state based on the probability of treatment success with the respective treatment. Clinical parameters and health utility data were sourced from the Acthar Gel in Participants with Pulmonary Sarcoidosis (PULSAR) trial (NCT03320070) and healthcare utilization, costs, and disutilities were sourced from the published literature. Base case analysis considered a payer perspective over 2 years. From a payer perspective, Acthar Gel versus SoC results in an incremental cost-effectiveness ratio (ICER) of $134,796 per quality-adjusted life-year (QALY) and $39,179 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $117,622 per QALY and $21,967 per QALY over 2 and 3 years, respectively. Sensitivity analysis findings were consistent with the base case. The results from this cost-effectiveness analysis indicate that Acthar Gel is a cost-effective, value-based treatment option for advanced symptomatic sarcoidosis compared to the SoC from the US payer and societal perspectives.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Corticosteroid Use and Adherence in Patients Treated with Acthar Gel for Advanced Sarcoidosis.

Long-term corticosteroid use in immune-mediated diseases is associated with increased risk of adverse events (AEs) and worsened health-related quality of life (HRQoL). Previous studies report chronic high-dose corticosteroid therapy results in higher rates of healthcare resource use and AE-related medical costs. Recent studies suggest Acthar® Gel (repository corticotropin injection) is an effective steroid-sparing therapy for sarcoidosis. This study compares the corticosteroid-sparing effect between Acthar Gel and comparators and evaluates the impact of Acthar Gel adherence on reduction of corticosteroid burden. A retrospective analysis of a large administrative pharmacy and medical claims database (Symphony Health Solutions) was conducted. Patients were included with confirmed ICD-9/10 diagnosis for sarcoidosis in the study period (2014-2020), followed by ≥ 2 Acthar Gel claims or comparators (janus kinase inhibitor (JAKi)/rituximab), ≥ 18years old, with 12months coverage pre/post index. Outcomes were compared as change from baseline. Acthar Gel adherence was determined by proportion of days covered in the follow-up period. The Acthar Gel (n = 735) and comparator (n = 626) cohorts were mostly female (68-72%) between 55 and 58years old. Compared to the comparator cohort at baseline, Acthar Gel patients had greater any corticosteroid use (80% vs. 56%, p < 0.001), extended use (61% vs. 32%, p < 0.001), and mean average daily dose (6.72 vs. 3.03, p < 0.001). After treatment, Acthar Gel patients had greater reduction from baseline in any corticosteroid use (-9.0% vs. -3.2%) and extended use (-10.0% vs. -3.0%). In the Acthar Gel adherence cohorts, patients with above average adherence had greater reduction in both measures (-11.2% vs. -6.1%; -11.6% vs. -7.6%, respectively) than patients with below average adherence. Acthar Gel patients had greater reduction of extended use at all dose levels. Acthar Gel is associated with reductions in corticosteroid use compared to alternatives. Better adherence is associated with greater reduction in corticosteroid exposure. Key Summary Points.

A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis.

Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP. Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer thickness (GC + IPL) were serially evaluated by OCT. In addition, patient-reported outcomes (PROs) for changes in fatigue, mood, visual function, depression, and quality of life (QOL) were measured, and high and low contrast visual acuity were recorded. Thirty-seven subjects were enrolled (19 RCI; 18 IVMP); the average time from symptom to treatment was 8.8 days. At 6 months, there was no difference in the primary outcome: loss of average pRNFL thickness in the affected eye (RCI vs IVMP: -13.1 vs -11.7 µm, P = 0.88) 6 months after randomization. Additional outcomes also showed no difference between treatment groups: 6-month attenuation of GC + IPL thickness (RCI vs IVMP: -13.8 vs -12.0 µm, P = 0.58) and frequency of pRNFL swelling at 1 month (RCI vs IVMP: 63% vs 72%, P = 0.73) and 3 months (RCI vs IVMP: 26% vs 31%, P = 0.99). Both treatments resulted in improvement in visual function and PROs. Treatment of acute optic neuritis with RCI or IVMP produced no clinically meaningful differences in optic nerve structure or visual function.

Acthar Gel (RCI): A Narrative Literature Review of Clinical and Economic Evidence.

Acthar® Gel (repository corticotropin injection [RCI]) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides used to treat patients with serious and rare inflammatory and autoimmune conditions. This narrative review summarizes the key clinical and economic findings among 9 indications: infantile spasms (IS), multiple sclerosis (MS) relapses, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis and polymyositis (DM/PM), ocular inflammatory diseases (primarily uveitis and severe keratitis), symptomatic sarcoidosis, and proteinuria in nephrotic syndrome (NS). Key studies of clinical efficacy and healthcare resource utilization and cost from 1956 to 2022 are discussed. Evidence supports the efficacy of RCI across all 9 indications. RCI is recommended as first-line treatment for IS and is associated with improved outcomes for the other 8 indications, including increased recovery rates in MS relapse; improved disease control in RA, SLE, and DM/PM; real-world effectiveness in patients with uveitis and severe keratitis; improved lung function and reduced corticosteroid use in symptomatic sarcoidosis; and increased rates of partial remission of proteinuria in NS. For many indications, RCI may improve clinical outcomes during exacerbations or when conventional treatments have failed to show a benefit. RCI is also associated with a reduction in the use of biologics, corticosteroids, and disease-modifying antirheumatic drugs. Economic data suggest RCI is a cost-effective, value-based treatment option for MS relapse, RA, and SLE. Other economic benefits have been demonstrated for IS, MS relapses, RA, SLE, and DM/PM, including reduced hospitalizations, lengths of stay, inpatient and outpatient services, and emergency department visits. RCI is considered safe and effective and features economic benefits for numerous indications. Its ability to control relapse and disease activity makes RCI an important nonsteroid treatment option that could help preserve functioning and well-being among patients with inflammatory and autoimmune conditions.

Acthar Gel Inhibits the Activation of CD4+ and CD8+ T Cells.

Several inflammatory diseases are characterized by elevated T cell counts and high pro-inflammatory cytokine levels. Inhibiting T cell activity may reduce tissue damage associated with these diseases. Acthar® Gel has potent anti-inflammatory properties, yet little is known about its effect on T cells. This study compared the effects of Acthar, synthetic adrenocorticotropic hormone 1-24 (ACTH1-24) depot, and prednisolone in a murine model of T cell activation. Assessments of CD4+ helper and CD8+ cytotoxic T cells and plasma concentrations of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) were made following anti-CD3-activation. Acthar significantly reduced the number of activated CD4+ and CD8+ T cells at amounts comparable to synthetic ACTH1-24 depot or prednisolone. However, Acthar reduced production of IFN-γ, IL-2, and TNF-α significantly more than the other drugs, suggesting that the in vivo immunomodulatory effects of Acthar on T cells are distinct from synthetic ACTH1-24 depot or prednisolone.

A Narrative Review of Acthar Gel for the Treatment of Myositis.

Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders characterized by symmetric proximal muscle weakness and chronic inflammation, with an increased risk of morbidity and mortality. The current standard of care includes traditional immunosuppressive pharmacotherapies; however, some patients cannot tolerate or do not adequately respond to these therapies, highlighting the need for alternative treatments for refractory disease. Acthar® Gel (repository corticotropin injection) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that has been approved by the US Food and Drug Administration since 1952 for use in patients with two subgroups of IIMs, dermatomyositis (DM) and polymyositis (PM). However, it has not been routinely used in the treatment of IIMs. While Acthar may induce steroidogenesis, it also has a steroid-independent mechanism of action by exerting immunomodulatory effects through the activation of melanocortin receptors on immune cells, such as macrophages, B cells, and T cells. Recent clinical trials, retrospective analyses, and case reports add to the growing evidence suggesting that Acthar may be effective in patients with DM and PM. Here we review the current evidence supporting the safety and efficacy of Acthar for the treatment of refractory DM and PM.

Hematopoietic-specific melanocortin 1 receptor signaling protects against nephrotoxic serum nephritis and mediates the beneficial effect of melanocortin therapy

The melanocortin hormone system has emerged as a novel therapeutic target for treating refractory glomerular diseases. However, the role of hematopoietic melanocortin 1 receptor (MC1R) signaling remains unknown. Upon insult by rabbit nephrotoxic serum, MC1R null-mutant mice developed more severe crescentic glomerulonephritis than wild-type mice, marked by aggravated proteinuria, kidney dysfunction and histologic lesions. Melanocortin therapy, using Repository Corticotropin Injection (Acthar Gel), the pan-melanocortin receptor agonist NDP-MSH, or the MC1R agonist MS05, ameliorated experimental nephritis in wild-type mice but this effect was blunted in null mice. Exacerbated experimental nephritis in null mice was associated with increased glomerular deposition of autologous IgG and C5b-9, in parallel with higher circulating levels of autologous IgG2c and IgG3. Additionally, the Th1 immune response was potentiated in null mice with experimental nephritis, accompanied by diminished kidney FoxP3+ regulatory T cells. Kidney infiltration of macrophages was also augmented by MC1R deficiency with an enhanced M1 polarization. Moreover, adoptive transfer of syngeneic bone marrow-derived cells from wild-type mice mitigated experimental nephritis in null mice and restored the beneficial efficacy of melanocortins. Mechanistically, MC1R was expressed by diverse subsets of kidney leukocytes, including macrophages, T and B lymphocytes, and was inversely associated with the NFκB pathway, a key player in immune responses. MS05 attenuated the production of rabbit IgG-specific IgG2c and IgG3 in cultured wild-type splenocytes, and promoted M2 polarization in M1-primed wild-type macrophages, associated with NFκB inhibition. In contrast, in null splenocytes or macrophages, this effect of MS05 was barely detectable, but was mimicked by an NFκB inhibitor. Thus, hematopoietic MC1R signaling attenuates experimental nephritis and mediates the beneficial effect of melanocortin therapy via, in part, regulating the immune response.

Cost-Effectiveness of Acthar Gel Versus Standard of Care for the Treatment of Exacerbations in Moderate-to-Severe Systemic Lupus Erythematosus.

Despite current standard of care (SoC), there is an unmet need for the treatment of active systemic lupus erythematosus (SLE). The study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC treatment in patients with active, moderate-to-severe SLE from the US payer and societal perspectives over 2 and 3 years. Cost-effectiveness model was developed using a probabilistic cohort-level state-transition approach. Patients received Acthar Gel in an exacerbation state, and the outcomes were assessed at the end of a 3-month cycle for response achievement based on the probability of treatment success with Acthar Gel. Patients may sustain the response or experience an exacerbation. For the base case scenario, moderate-to-severe SLE was defined as British Isles Lupus Assessment Group (BILAG)-2004 ≥ 20 or SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 10 and clinical response was based on SLE responder index (SRI)-4. Clinical response, productivity loss, and utility were derived from a phase 4 SLE trial; cost and disutility estimates were sourced from the literature. From a payer perspective, Acthar Gel versus SoC resulted in an incremental cost-effectiveness ratio (ICER) of $133,110 per quality-adjusted life-year (QALY) and $94,818 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $70,827 per QALY and $32,525 per QALY over 2 and 3 years, respectively. Results from the sensitivity and scenario analyses are consistent with those of the base case model. Acthar Gel is a cost-effective, value-based treatment option for appropriate patients with moderate-to-severe SLE at a willingness-to-pay threshold of $150,000 over 2-3 years from the US payer and societal perspectives. Acthar Gel results in the reduction of direct medical and indirect costs.

A Multicenter, Prospective, Open-Labeled Study of Acthar Gel Alone or with Tacrolimus to Reduce Urinary Proteinuria in Patients with Idiopathic DNA-JB9-Positive Fibrillary Glomerulopathy

A Multicenter, Prospective, Open-Labeled Study of Acthar Gel Alone or with Tacrolimus to Reduce Urinary Proteinuria in Patients with Idiopathic DNA-JB9-Positive Fibrillary Glomerulopathy

Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1-24 Depot and Methylprednisolone in Healthy Subjects.

Repository corticotropin injection (RCI; Acthar Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides. This phase 1, single‐center, open‐label, randomized parallel study directly compared the pharmacokinetics and pharmacodynamics of RCI and synthetic ACTH1‐24 depot. Methylprednisolone was included to estimate the steroidogenic exposure of RCI and synthetic ACTH1‐24 depot when used to treat nephrotic syndrome. A total of 48 healthy subjects aged 18 to 50 years were randomly assigned 1:1:1 to RCI (80 IU subcutaneously twice weekly on study days 1 and 4), synthetic ACTH1‐24 depot (1 mg subcutaneously twice weekly on study days 1 and 4), or methylprednisolone (32 mg orally once daily on study days 1 through 6). After 2 doses, RCI induced about 5‐fold lower free cortisol exposure and an estimated 4‐fold lower steroidogenic exposure than synthetic ACTH1‐24 depot. The lower endogenous cortisol response of RCI was achieved despite higher observed mean plasma concentrations of N25‐deamidated porcine ACTH1‐39 (the pharmacokinetic marker for RCI) than of ACTH1‐24. The different pharmacodynamic properties demonstrated by RCI and synthetic ACTH1‐24 depot in this study suggest that these products in the ACTH class are not interchangeable.

Practice patterns and outcomes of repository corticotropin injection (Acthar® Gel) use in childhood nephrotic syndrome: A study of the North American Pediatric Renal Trials and collaborative studies and the Pediatric Nephrology Research Consortium

Objective: We set up a U.S. registry to examine prescription patterns and patient outcomes of repository corticotropin injection (Acthar® Gel) for childhood nephrotic syndrome. Methods: 18 participating U.S. pediatric centers performed retrospective review and prospective observation of patients &lt; 21 years old with nephrotic syndrome treated with Acthar Gel. We captured baseline characteristics, drug regimen and duration, and disease response following treatment. Results: 46 patients, enrolled from 2015 to 2020 were included. 27 (58.7%) were male. 18 patients (39.1%) had a diagnosis of minimal change followed by focal segmental glomerulosclerosis in 16 patients (34.7%). Median age at start of treatment was 12.5 years (IQR 8.5-17.4) compared to 5.3 years at diagnosis (IQR 2.7-10.5 years). 52% were resistant to corticosteroids. The most common Acthar Gel regimen was 80IU twice a week with a median duration of 199 days (IQR 88-365). Among 37 patients with active disease, 18 (49%) were able to achieve partial or complete remission, though all patients that had a positive response were on other immunosuppressants concomitantly. Conclusion: We report the findings of the largest registry cohort of pediatric patients in the U.S. treated with Acthar Gel for clinically challenging cases of nephrotic syndrome. Acthar Gel was successful in inducing remission in approximately half of the patients with active disease at time of treatment. No predictors of response with respect to demographic data, age at start of Acthar Gel therapy, etiology of nephrotic syndrome, presence or absence of comorbidities, or steroid responsiveness was noted.

Repository Corticotropin Injections Promote Clinical Remission and Regulatory T Cell Expansion in Membranous Nephropathy

Repository Corticotropin Injections Promote Clinical Remission and Regulatory T Cell Expansion in Membranous Nephropathy

Consequences of insurance denials among U.S. patients prescribed repository corticotropin injection (Acthar Gel) for nephrotic syndrome

Introduction Repository corticotropin injection (RCI; Acthar Gel) is indicated to induce a diuresis or a remission of proteinuria in nephrotic syndrome (NS) without uremia of the idiopathic type or that due to lupus erythematosus. This study compares patient characteristics and measurable healthcare resource utilization (HCRU) between NS patients who received a prescription for RCI and then were either approved or denied treatment by their insurers. Methods A retrospective analysis of adults with NS from January 2015 to December 2018 was conducted using a de-identified open-source claims database. Patients were included in the study if they had ≥1diagnosis associated with NS, were age 18+, and had medical claims activity at some point in the year preceding (“baseline”) and year following (“follow up”) their first approved or denied RCI prescription. Baseline characteristics were reported with p-values indicating the significance of characteristics between cohorts. To assess outcomes, approved and denied patients were matched (1:1) using propensity-matching to account for underlying differences. Results Overall, 1,232 patients met inclusion criteria for the study. At baseline, approved patients were older than denied patients (mean age 53.9 vs. 48.4) and had higher rates of comorbidities. A greater proportion of approved patients required inpatient admissions (34.1 vs. 28.0%) and "high" doses of corticosteroids (CS) (26.2 vs. 20.7%) at baseline. Matched outcomes showed directionally more denied patients with inpatient admissions compared to approved (64 vs. 52) and a greater utilization of deep vein thrombosis ultrasound (12.2 vs. 6.6%) and dialysis (10.5 vs. 6.1%). Matched, denied patients had directionally greater CS use during follow-up both in the number of patients receiving CS (104 vs. 95) and the average annualized daily dose (4.1 vs. 3.4 mg). Conclusion Patients denied access to RCI treatment had directionally higher HCRU compared to matched, approved counterparts. Thus, the results of this study may aid providers and payers in evaluating scenarios where RCI may be beneficial and improve quality of care for NS patients.

Comparison of Steroidogenic Exposure Following the Administration of Repository Corticotropin Injection With a Synthetic ACTH1‐24 Depot and Methylprednisolone in Healthy Subjects

The pharmacokinetics (PK) and pharmacodynamics (PD) of clinically relevant doses of repository corticotropin injection (Acthar Gel) and synthetic ACTH1‐24 depot have not been fully characterized. We compared the steroidogenic exposure of repository corticotropin injection and synthetic ACTH1‐24 depot in healthy adults at therapeutic doses using data from 2 separate phase 1 studies. Subjects were randomly assigned to repository corticotropin injection 40 or 80 IU subcutaneously twice weekly or 80 IU subcutaneously 3 times weekly for 15 days or to daily synthetic ACTH1‐24 depot doses of 0.5 mg subcutaneously, 0.75 mg subcutaneously, 1 mg subcutaneously, or 1 mg intramuscularly for 5 days. A population PK/PD model was developed to simulate the free cortisol exposure of a clinically relevant dose of synthetic ACTH1‐24 depot (1 mg subcutaneously twice weekly). Study drug doses were converted to methylprednisolone‐equivalent doses using the steroidogenic exposure of methylprednisolone 16 mg daily as a conversion factor. Doses were also converted to prednisone equivalents using a coefficient of 1.25. These analyses revealed that the steroidogenic exposure of repository corticotropin injection at clinically relevant doses was substantially lower than that for synthetic ACTH1‐24 depot. The 3 repository corticotropin injection regimens were equivalent to approximately 5, 8, and 16 mg of daily prednisone, respectively. On the basis of simulated free cortisol exposure, synthetic ACTH1‐24 depot 1 mg subcutaneously twice weekly was comparable to 57 mg of daily prednisone. These results suggest that repository corticotropin injection has pharmacological effects that cannot be considered identical to synthetic ACTH1‐24 depot.

A Retrospective Study of Utilization of Repository Corticotropin Injection (HP Acthar Gel) as Pretreatment for Alemtuzumab Infusion

Background: Alemtuzumab treatment of patients with MS is associated with cytokine release, resulting in infusion-associated reactions (IARs). Premedication with corticosteroids is typically administered to alleviate the risk of IARs, but steroid pretreatment is not feasible in some patients. This study investigated real-world experience using repository corticotropin injection (RCI) as a pretreatment for alemtuzumab infusion. Methods: A retrospective study of patients who were prescribed RCI as pretreatment for the prevention of alemtuzumab IARs was conducted using an electronic questionnaire. Data were de-identified at the time of collection. Results: Complete information on 175 patients was collected and analyzed. Data for alemtuzumab Course 1 infusions were available for 175 patients; 23 of these also had data available for Course 2 infusions. Patients were 62% Caucasian, 21% black, 15% Hispanic, and were diagnosed with relapsing forms of MS (60%) or progressive forms of MS (40%). Reasons for using RCI prior to alemtuzumab included history of steroid intolerance (Course 1: 37%, Course 2: 59%), history of poor response to steroids (20%, 27%), and comorbidities (20%, 27%). RCI was most frequently administered subcutaneously at a dose of 80 units. No IARs occurred in 56% (Course 1) and 61% (Course 2) of patients after RCI pretreatment. No adverse events attributed to RCI were seen in 72% and 91% of patients treated with Course 1 and 2, respectively. Conclusion: RCI is a safe, effective, and well-tolerated pretreatment alternative to corticosteroids to alleviate the risk of alemtuzumab-associated infusion reaction in patients with MS.