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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function.

INTRODUCTION: Hepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective. METHODS: A decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated. RESULTS: Cost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively. CONCLUSIONS: The analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.

Hepatorenal syndrome, a functional, progressive kidney failure, is a life-threatening complication of cirrhosis. It is important to improve kidney function in patients who are hospitalized with hepatorenal syndrome considering the cost of treatment. This study assessed the cost per complete response/ hepatorenal syndrome reversal of terlipressin + albumin from a United States hospital perspective. This study shows that terlipressin improves kidney function with lower intensive care unit and dialysis costs compared with unapproved treatments. Terlipressin is a cost-effective, value-based treatment option for appropriate adults with hepatorenal syndrome with rapid reduction in kidney function.

Cost-effectiveness of terlipressin for hepatorenal syndrome: the United States hospital perspective.

BACKGROUND: Hepatorenal syndrome (HRS) is characterized by severely reduced renal perfusion that precipitates rapid morbidity and mortality. Terlipressin is the only US Food and Drug Administration-approved treatment to improve kidney function for adults with HRS with a rapid reduction in kidney function. Prior to the approval of terlipressin, unapproved vasoconstrictive agents used in HRS treatment were octreotide/midodrine and norepinephrine with albumin. METHODS: A cohort decision-tree model representing a US hospital perspective assessed the clinical outcomes and direct medical costs (based primarily on hospital charges) of treating HRS with terlipressin + albumin (ALB) versus midodrine/octreotide (MID/OCT)+ALB, or norepinephrine (NorEp)+ALB. Treatment efficacy was defined by clinical response (complete/HRS reversal, partial, or no response) based on change of serum creatinine derived from published clinical trial reports. The proportions of patients with complete response were: terlipressin + ALB (36.2%), NorEp + ALB (19.1%), and MID/OCT + ALB (3.1%). Model outcomes included utilization of HRS-related healthcare resources (hospital and intensive care, outpatient and emergency department, dialysis, and transplantations), adverse events, and HRS-related mortality. Outcomes were assessed for the initial hospitalization in the base case and at 30, 60, and 90 days post-discharge. RESULTS: Total costs incurred over the initial hospitalization with terlipressin + ALB were lower vs NorEp + ALB, primarily due to higher ICU costs with NorEp + ALB ($7,433 vs $61,897). TER + ALB was associated with higher total costs vs MID/OCT + ALB due to higher pharmacy costs with terlipressin + ALB. The cost per complete response achieved of terlipressin + ALB ($451,605) was half that of NorEp + ALB ($930,571) and one-tenth that of MID/OCT + ALB ($4,942,123). CONCLUSIONS: HRS patients treated with terlipressin experienced better clinical outcomes and a lower cost per treatment response vs other unapproved treatments. ICU days and pharmacy costs were key cost drivers distinguishing the treatment groups. These outcomes suggest that terlipressin is cost-effective on the basis of total cost per response achieved.

Hepatorenal syndrome (HRS) is a rare and sudden life-threatening complication of the liver. Patients with HRS should receive immediate treatment with a drug that narrows blood vessels known as a vasoconstrictor. Terlipressin is the most common vasoconstrictor used for patients with HRS. Other common vasoconstrictors are midodrine with octreotide and norepinephrine. This study aimed to compare the cost of terlipressin with those of midodrine with octreotide and norepinephrine while also considering how well each of them worked to reverse HRS. This was done using an economic model. This economic model assessed the costs of the vasoconstrictor drugs and the costs of treating HRS, including costs attributable to drug acquisition, adverse events, organ transplantation, dialysis, and institutional encounters (i.e. hospitalization, ICU, emergency department, and outpatient visits). The magnitude of these costs depends on how well each drug reversed HRS. Based on inputs derived from their respective clinical trials, 36% of patients who were given terlipressin had a complete response (HRS was reversed), 19% of patients who were given norepinephrine had a complete response, and 3% of patients who were given midodrine with octreotide had a complete response. The total cost per patient was approximately $163,481 for terlipressin, $177,298 for norepinephrine, and $155,030 for midodrine with octreotide. When the costs were evaluated against how well the drugs worked to reverse HRS, the lowest cost per HRS reversal was $451,605 when treated with terlipressin. The cost per reversal for norepinephrine was $930,571 and for midodrine with octreotide was $4,942,123. These results show that terlipressin works well and is more cost-effective for US hospitals compared with the other unapproved treatment options for HRS with rapid reduction in kidney function.

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

INTRODUCTION: 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. METHODS: 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), ≥ 18 years old, with 12 months 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. RESULTS: The Acthar Gel (n = 735) and comparator (n = 626) cohorts were mostly female (68-72%) between 55 and 58 years 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. CONCLUSION: 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.

Patients who use corticosteroids long term for advanced sarcoidosis often suffer from negative health effects. This project aimed to evaluate whether Acthar^® Gel (repository corticotropin injection) use led to reduced corticosteroid use and whether higher adherence to Acthar Gel led to further reduction in corticosteroid use. Pharmacy and medical claims data were used to identify patients who fit certain criteria: the Acthar Gel cohort included patients with sarcoidosis who used Acthar Gel and the comparator cohort included patients with sarcoidosis who used janus kinase (JAK) inhibitors or rituximab. The Acthar Gel cohort was split into high adherence and low adherence. The Acthar Gel cohort was found to have higher corticosteroid use than the comparator group in the baseline period before initiating Acthar Gel or a comparator therapy. After initiating treatment, Acthar Gel patients had a larger reduction in corticosteroid use according to a variety of metrics including number of corticosteroid fills and extended use fills. Furthermore, when comparing those with high Acthar Gel adherence and those with low Acthar Gel adherence, the patients with above average adherence had a larger reduction in the number of corticosteroid fills and extended use fills than patients with below average adherence to Acthar Gel. Patients who use Acthar Gel and more regularly tended to use corticosteroids less, which may allow them to avoid the negative health effects from long-term, high-dosage corticosteroid use. This finding may help providers and health plans evaluate situations in which Acthar Gel treatment may be beneficial to improve patient outcomes.

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.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pain and Fatigue Improvements in Patients Treated with Repository Corticotropin Injection Across Five Indications: A Narrative Review.

Repository corticotropin injection (RCI; Acthar® Gel) is approved by the US Food and Drug Administration (FDA) for use in 19 indications, including for the treatment of selected patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), symptomatic sarcoidosis, uveitis, and keratitis. Despite treatment with disease-modifying antirheumatic drugs, many patients with RA, SLE, and other chronic inflammatory rheumatic diseases continue to be affected by severe pain and fatigue, indicating a need for other therapies. To examine the clinical data regarding the impact of RCI treatment on pain and fatigue in selected populations, this review included English-language peer-reviewed publications of clinical trials of any size and cohort studies with more than 10 patients that included pain and/or fatigue based on patient-reported outcomes (PROs) and/or physician-assessed measures in adults following treatment with RCI for RA, SLE, symptomatic sarcoidosis, uveitis, or keratitis. Literature searches identified eight studies that met these criteria. Four studies (reported in five publications) were in patients with RA or SLE, two in patients with sarcoidosis, one in patients with uveitis, and one in patients with noninfectious keratitis. Across the different types of studies assessed (clinical trials, chart reviews, real-world evidence), the results were consistent with respect to the impact of RCI treatment on improving pain and fatigue. As summarized in this review, data from patient- and physician-reported outcome measures in eight studies demonstrate that, in addition to improving more traditional efficacy measures, RCI may also improve pain and fatigue in patients with RA, SLE, symptomatic sarcoidosis, uveitis, and noninfectious keratitis.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases. Clinical studies of drugs for these diseases do not often ask patients how they feel after treatment. Despite treatment, many people with these diseases have pain and feel tired. Repository corticotropin injection (RCI) is a prescription drug for patients with RA, SLE, and other chronic immune diseases. We reviewed the results of published studies with data on pain and fatigue from patients treated with RCI. Four studies were in patients with RA or SLE. Two studies were in patients with symptomatic sarcoidosis. One study was in patients with uveitis. One study was in patients with noninfectious keratitis. These eight studies show that adding RCI to standard treatment lowers pain and fatigue in some patients. It would be helpful to measure pain and fatigue in future clinical studies of drugs for patients with chronic immune diseases.

Understanding Predictors of Response to Repository Corticotropin Injection Treatment Among Patients With Advanced Symptomatic Sarcoidosis.

Background: Sarcoidosis, an inflammatory systemic granulomatous disease, affects multiple organs and has a diverse clinical course. Repository corticotropin injection (RCI) is an effective treatment for advanced symptomatic sarcoidosis. Since sarcoidosis affects patients differently, treatment response may vary by patient demographic, clinical, and treatment-related characteristics and physician specialty. However, there is a paucity of literature regarding predictors of sarcoidosis treatment response. Objectives: This study investigated predictors of response to RCI treatment. Methods: Post-hoc analysis was conducted using data from a previously published retrospective cross-sectional chart review study among symptomatic sarcoidosis patients ≥18 years of age previously treated with RCI. Outcome improvement 3 months post-RCI treatment was based on the clinician's subjective evaluation and analyzed using adjusted logistic regression. The most influential predictors for each outcome were based on statistical significance (P<.05) and the strength of the relationship assessed by the standardized ß coefficients. Results: The top predictors of outcome improvements were as follows. Global health assessment: (1) improvement in current health status influenced by complete RCI compliance, moderate overall symptom severity, and presence of extrapulmonary sites; and (2) improvement in overall symptoms influenced by age, shorter duration since sarcoidosis diagnosis, and complete RCI compliance. Clinical outcomes: (1) lung function improvement influenced by mild weight loss, mild wheezing/coughing, and non-African American race; (2) reduction in pulmonary fibrosis influenced by moderate overall symptom severity, mild wheezing/coughing, and mild weight loss; and (3) reduction in inflammation influenced by physician specialty, completing a course of RCI treatment, and moderate-to-severe night sweats. Patient-related outcomes: (1) reduction in fatigue influenced by physician specialty and moderate-to-severe fatigue; and (2) improvement in quality-of-life influenced by shorter duration since sarcoidosis diagnosis, moderate-to-severe wheezing/coughing, and complete RCI compliance. Corticosteroid discontinuation/reduction was influenced by physician specialty, moderate-to-severe shortness of breath, and comedication use before RCI. Conclusions: RCI may be a better treatment option for patients with more severe disease, primarily those presenting with symptoms. Complete compliance with RCI treatment may improve patients' health and quality of life. Understanding factors that influence RCI effectiveness across different treatment outcomes in real-world clinical practice is important for designing optimal sarcoidosis treatment strategies.

Real-world treatment patterns for repository corticotropin injection in patients with rheumatoid arthritis.

Introduction: Repository corticotropin injection (RCI, Acthar® Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogues and other pituitary peptides with anti-inflammatory and immunomodulatory effects. In a recent clinical trial, RCI was safe and effective for the treatment of refractory rheumatoid arthritis (RA). This study aims to describe real-world use and outcomes of patients with RA who were prescribed RCI in clinical practice through retrospective analysis of an electronic medical record database. Methods: Patients with RA who were prescribed RCI were identified through the ColumbusTM electronic medical record repository, representing approximately 100 rheumatology practices. Demographics, medications, comorbidities, disease histories, laboratory evaluations, clinical outcomes and patient-reported outcomes were evaluated from 12 months pre-RCI to 12 months post-RCI initiation. Results: The RCI cohort (n=63) comprised predominantly white women, aged 54 years on average, at 6 years from RA diagnosis, with high disease activity at baseline according to Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) scores. Within the 12 months pre-RCI initiation, 87% of patients were prescribed disease-modifying antirheumatic drugs and 67% were prescribed glucocorticoids. Twelve months post-RCI initiation, glucocorticoid, opioid and non-steroidal anti-inflammatory drug prescriptions decreased; disease-modifying antirheumatic drug prescriptions remained stable. Reductions in CDAI, RAPID3, physician global assessment, tender joint count, swollen joint count, and pain visual analogue scale scores were observed 12 months post-RCI initiation. Few discontinuations were due to side effects. Study limitations included small sample size and incomplete electronic medical record data. Conclusion: These findings support the safety and effectiveness of RCI for short-term adjunctive treatment of refractory RA and provide patient-management insights from routine clinical practice.

Cost-Effectiveness of Repository Corticotropin Injection for the Treatment of Acute Exacerbations in Multiple Sclerosis.

BACKGROUND: Relapses are common among patients with multiple sclerosis (MS) despite treatment with disease-modifying therapies. Repository corticotropin injection (RCI, Acthar® Gel), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) are alternative therapies for MS relapse. There is a dearth of economic assessments of these therapies for the acute exacerbations of MS. This study estimated the cost-effectiveness of RCI compared to PMP or IVIg. METHODS: A Markov state-transition model compared outcomes (costs, relapses, remission, and utilities) with RCI versus PMP or IVIg for the acute exacerbations in MS. The model was developed from the United States (US) payer and societal perspectives over one to three years. Patients initiated on alternative therapies were evaluated in one-day increments for the first 30 days during treatment. The model assumes the natural history of MS after treatment in the first month, adjusting for the effect of treatment. Incremental cost-effectiveness ratios (ICERs) were estimated as cost per quality-adjusted life-year (QALY) gained. The uncertainty in model parameters was evaluated in probabilistic sensitivity analyses. RESULTS: In the base case, RCI has an ICER of USD 42,078 per QALY compared to PMP over one year from the payer perspective and is dominant over two and three years; RCI is dominant compared to PMP from the societal perspective over all three years. Compared to IVIg, RCI is a dominant strategy from both payer and societal perspectives over all three years. Probabilistic sensitivity analysis supports the base case findings, suggesting that RCI may be cost-effective versus PMP and IVIg for acute exacerbations in MS. CONCLUSION: RCI is a cost-effective alternative treatment for MS relapses compared to PMP and IVIg from the US payer and societal perspectives.

Real-World Treatment Patterns and Outcomes from an Electronic Medical Records Database for Patients with Rheumatoid Arthritis Treated with Repository Corticotropin Injection.

PURPOSE: Repository corticotropin injection (RCI; Acthar® Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that exerts anti-inflammatory and immunomodulatory properties via melanocortin receptors. RCI is approved as a short-term adjunctive therapy for rheumatoid arthritis (RA) and is typically used in patients with refractory RA. The objective of this study was to describe real-world outcomes of RA patients treated with RCI by retrospective analysis of an electronic medical records (EMR) database. PATIENTS AND METHODS: EMR data were obtained from the United Rheumatology-Normal Integrated Community Evidence (UR-NICETM) data repository for patients who used RCI for the treatment of RA. Demographics, comorbidities, disease history, medications, and laboratory evaluations 365 days prior to and 365 days after initiation of RCI were examined. RESULTS: The patient cohort was predominantly White females with a mean age of 60 years and high RA activity prior to RCI therapy. Clinical measures of disease severity indicated that patients had high RA activity before starting RCI therapy. Clinical Disease Activity Index (CDAI) scores were significantly reduced 365 days post-initiation of RCI. Swollen and tender joint counts and patient-reported outcomes, including Routine Assessment of Patient Index Data 3 (RAPID3), Physician Global Assessment, and patient assessment of pain severity were also significantly lower. The number of patients taking conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), biologic (b) DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDS), and opioids decreased, as did the number of drugs tried within each class for csDMARDs, bDMARDs, NSAIDs, and glucocorticoids. CONCLUSIONS: These findings suggest that RCI significantly improves clinical outcomes of RA and decreases the need for concomitant medications for up to 1 year following initiation of therapy. The study provides valuable insights into the use of RCI and management of these difficult-to-treat RA patients during routine clinical practice.

Cost-Effectiveness of Repository Corticotropin Injection versus Standard of Care for the Treatment of Active Rheumatoid Arthritis.

INTRODUCTION: Patients with active rheumatoid arthritis (RA) often have inadequately controlled symptoms and are unable to achieve remission or low disease activity despite aggressive treatment. This results in irreversible joint damage, adversely affecting patients' physical and social functioning. The objective was to estimate the cost-effectiveness of repository corticotropin injection (RCI) versus standard of care (SoC) in patients with active RA from the United States (US) payer and societal perspectives over two to three years. METHODS: An individual-level microsimulation was developed to generate individual trajectories for patients with RA, using data from a published Phase 4 trial of RCI. These trajectories report a patient's disease pathway and associated cost and quality-of-life outcomes. The incremental cost-effectiveness ratio (ICER) of RCI versus SoC was assessed using the literature-derived direct medical and indirect costs, and quality-adjusted life-years (QALY) derived from a Phase 4 trial of RCI. The uncertainty in base case estimates of the parameters was evaluated in the sensitivity analysis. RESULTS: Over two years, RCI has an incremental QALY gain of 1.591 and incremental cost of $183,965 and $117,443 from payer and societal perspective, respectively, resulting in an ICER of $115,629/QALY and $73,817/QALY compared to SoC. Over three years, RCI has an incremental QALY gain of 2.336 and incremental cost of $202,315 and $104,506 from payer and societal perspective, respectively, resulting in an ICER of $86,607/QALY and $44,737/QALY compared to SoC. Results from the probabilistic sensitivity analysis are consistent with those of the base case model. CONCLUSION: RCI is a cost-effective strategy for patients with persistently active RA who are previously treated with disease-modifying anti-rheumatic drugs and corticosteroids compared to SoC over two to three years from the payer and societal perspectives at a US willingness-to-pay threshold of $150,000/QALY. Further, the economic benefit of RCI is realized with improvement in a patient's clinical and health outcomes.

A Systematic Literature Review and Indirect Treatment Comparison of Efficacy of Repository Corticotropin Injection versus Synthetic Adrenocorticotropic Hormone for Infantile Spasms.

Background: Infantile spasms is a rare disease characterized by distinct seizures and hypsarrhythmia. Adrenocorticotropic hormone (ACTH) is available as a natural product (repository corticotropin injection, [RCI]; Acthar® Gel) and as synthetic analogs. RCI is a naturally-sourced complex mixture of purified ACTH analogs and other pituitary peptides approved by the United States Food and Drug Administration as a monotherapy for the treatment of infantile spasms. RCI is commonly used in the United States. Outside the United States, synthetic analogs of ACTH-synthetic ACTH1-24 (tetracosactide) and synthetic ACTH1-39 (corticotropin carboxymethyl-cellulose [CCMC])-are used. The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; however, no head-to-head clinical trials have compared the efficacy of RCI and synthetic ACTH treatments. Objective: A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms. Methods: A search was conducted in MEDLINE, EMBASE, and Cochrane databases through September 30, 2020. Relevant clinical trials on RCI or synthetic ACTH therapy and reporting either cessation of spasms or resolution of hypsarrhythmia, separately or as a combined outcome were included. A Bayesian indirect treatment comparison using a fixed-effects model was used for comparative efficacy. Results: Of 473 citations screened, 21 studies were reviewed qualitatively. In the indirect treatment comparison of six eligible clinical trial studies, the odds of achieving efficacy outcomes were five to eight times greater with RCI than with tetracosactide and 14 to 16 times greater than CCMC. This translated to a risk reduction of 10% to 14% and 40% to 50% with RCI versus tetracosactide and CCMC, respectively. For every two to five patients treated, RCI improved efficacy outcomes in one additional patient compared to synthetic ACTH (adjusted number needed-to-treat). Conclusions: Based on the available limited evidence, results suggest RCI may be more efficacious for infantile spasms than synthetic ACTH treatments. Our findings provide a blueprint to inform the design of future prospective studies for the treatment of infantile spasms.

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.

Consequences of Insurance Denials Among U.S. Patients Prescribed Repository Corticotropin Injection for Acute Exacerbations of Multiple Sclerosis.

INTRODUCTION: Repository corticotropin injection (RCI; Acthar® Gel) is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Despite the well-documented clinical and economic benefits of RCI, many patients are denied use of the therapy by third-party payers. This study aims to understand the demographic and clinical characteristics of MS relapse patients who received a prescription for RCI from their physicians and then were either approved or denied treatment by their insurers. The study compares measurable clinical outcomes and healthcare resource utilization (HCRU) between approved and denied cohorts. METHODS: A retrospective analysis of adults experiencing MS relapse from January 2015 to December 2018 was conducted using a de-identified open-source claims database [Symphony Health Integrated Dataverse® (IDV)]. Patients were identified using ICD codes for MS and considered to have relapsing/remitting type according to established claims-based methodology. Clinical characteristics and HCRU were analyzed during the year preceding ("baseline") and the year following ("follow-up") each patient's index date, defined as the date of a patient's first approved RCI claim (for patients with ≥ 1 approved claim) or first denied RCI claim (for patients with only denied claims). Baseline characteristics were reported with unadjusted differences and p values indicating the significance of characteristics between the two cohorts. For outcomes, match-adjusted results were reported using propensity matching to account for underlying differences between cohorts. RESULTS: The study sample included 1902 MS relapse patients with at least one claim for RCI. At baseline, approved patients were slightly older compared to denied patients (mean age 48.0 vs. 47.2), had higher rates of hemiplegia/paraplegia (6.7% vs. 3.3%), greater mobility impairment (17% vs. 11.5%), more exacerbation episodes (66.2% vs. 59.9%), and a higher number of physical therapy/rehab claims (23.5 vs. 14.0), respectively. Outcomes among the matched sample show an increased use of corticosteroids for patients denied access to RCI compared to approved patients (51.1% vs. 42.4%), more exacerbation episodes (36.6% vs. 28.2%), and an increased number of physical therapy/rehab claims (11.5% vs. 9.9%), respectively. CONCLUSION: The results of this study may aid providers and payers in evaluating scenarios where RCI may be beneficial and improve quality of care for patients experiencing MS relapse.

Cost per response analysis of repository corticotropin injection versus other alternative treatments for acute exacerbations of multiple sclerosis.

BACKGROUND: Relapses are common in patients with multiple sclerosis (MS) even after the use of disease-modifying therapies. Repository corticotropin injection (RCI), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) may be utilized as alternative therapies in the management of MS relapse. There is a lack of health economic studies on these alternative therapies for the acute exacerbations of MS. The objective of this study was to estimate the cost per response of RCI compared with PMP or IVIg from the United States (US) commercial payer perspective. METHODS: Costs and response rates were sourced from published peer-reviewed observational studies. The cost of care included MS-related inpatient, outpatient, and medication costs. Treatment response was defined as no evidence of additional relapse treatment or procedure claims within 30 days after treatment. The cost per response for each treatment was calculated by dividing the total annual cost of care by the proportion of patients with resolved relapse for each treatment. The incremental cost per response ratio was calculated by dividing the difference in costs and the proportion of responses for RCI versus PMP or IVIg. One-way sensitivity analysis (OWSA) was conducted for both costs and response rates. All included costs were inflated to the 2019 US dollars. RESULTS: With a lower total annual cost of care and a higher response rate, RCI had a lower cost per response (US$141,970) compared with PMP or IVIg (US$253,331). RCI had a lower cost per response even when more stringent estimates for RCI were applied in the OWSA. The annual cost of care had a greater influence on the cost per response in the OWSA. CONCLUSIONS: Based on the estimates from the real-world evidence, our economic evaluation suggests that RCI may have real-world clinical and economic benefits for patients with MS relapse who fail on corticosteroid therapy.

Clinical and Economic Evaluation of Repository Corticotropin Injection: A Narrative Literature Review of Treatment Efficacy and Healthcare Resource Utilization for Seven Key Indications.

INTRODUCTION: Repository corticotropin injection (RCI; H.P. Acthar® Gel; Mallinckrodt Pharmaceuticals Inc., Hampton, NJ) is a highly purified, prolonged-release porcine preparation of adrenocorticotropic hormone (ACTH) analogue that is FDA-approved for treatment of 19 autoimmune and inflammatory disorders. The diverse physiological actions of RCI at the melanocortin receptors (MCRs) affect processes involved in inflammation, pigmentation, steroidogenesis, and immunomodulation. Although RCI has been approved to treat inflammatory and autoimmune diseases for more than 60 years, recent progress in understanding both MCRs and the effects of RCI in modulating immune responses has led to increased interest in RCI as a therapeutic choice. The objective of this narrative literature review is to summarize key clinical and economic data on RCI treatment of seven disorders: infantile spasms (IS), multiple sclerosis (MS) relapses, proteinuria in nephrotic syndrome, rheumatoid arthritis (RA), dermatomyositis/polymyositis (DM/PM), systemic lupus erythematosus (SLE), and symptomatic sarcoidosis based on published literature and product information. An extended report is available as the Academy of Managed Care Pharmacy (AMCP) Formulary dossier for H.P. Acthar® Gel. METHODS: Key studies of clinical efficacy and healthcare utilization and cost from 1956 to 2016 are summarized. RESULTS: The evidence supports the efficacy of RCI across the seven indications. RCI is effective as a first-line therapy for IS. For the other six conditions, RCI may improve clinical outcomes during exacerbations or when the condition is resistant to conventional treatments. Use of RCI is associated with reduced use of biologics, corticosteroids, and disease-modifying antirheumatic drugs. Initiation of RCI therapy in patients with IS, MS, RA, SLE, or DM/PM has been associated with lower post-therapy healthcare utilization and medical costs, including decreases in hospitalizations, hospital length of stay, outpatient visits, and emergency department visits. CONCLUSION: The evidence suggests that RCI may improve inflammatory and autoimmune disease control and patient quality of life, particularly in complex patients, and yield healthcare cost savings that demonstrate the medicine's value. FUNDING: Mallinckrodt Pharmaceuticals Inc.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

BACKGROUND: Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. METHODS: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. RESULTS: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). CONCLUSION: Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.

Healthcare Costs and Resource Utilization in Patients with Infantile Spasms Treated with H.P. Acthar Gel(®).

INTRODUCTION: The purpose of this study was to describe healthcare resource utilization and costs resulting from early (within 30 days of diagnosis) versus late (>30 days after diagnosis) treatment with prescriptions for H.P. Acthar(®) Gel (repository corticotropin injection; Acthar; Mallinckrodt) to manage infantile spasms (IS). METHODS: We included all patients in the Truven Health MarketScan(®) Commercial Claims and Encounters Database and the Truven Health MarketScan Multi-State Medicaid Database who were diagnosed with IS from 2007 to 2012. We performed unadjusted and adjusted regressions examining the relationship between healthcare resource utilization variables and their associated costs to compare outcomes in the early and late Acthar users. RESULTS: A total of 252 patients with IS who received Acthar fit our study criteria; 191 (76%) were early Acthar users. In adjusted analyses, we found that early Acthar use was associated with, on average, 3.8 fewer outpatient services (99% CI 0.7-6.7 fewer services). We did not find significant associations between early prescriptions for Acthar and number of hospitalizations, emergency room visits, prescription medications filled, or total costs of health services. CONCLUSION: Patients prescribed Acthar within 30 days of their IS diagnoses tended to have fewer outpatient services performed compared to patients prescribed Acthar later in the disease process. Although additional research is needed to confirm these exploratory findings, physicians may consider early treatment with Acthar to manage IS. FUNDING: This study was funded by a grant to the University of Washington from Mallinckrodt Pharmaceuticals.