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

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.

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.

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.

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.

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 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.

Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.

INTRODUCTION: Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. RESULTS: Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. CONCLUSIONS: RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03320070.

Pulmonary sarcoidosis is a disease characterized by inflammation of the lungs. Standard treatments include glucocorticoids, which may have harmful side effects. This clinical trial investigated whether repository corticotropin injection (RCI, Acthar^® Gel) was safe and effective in patients who were already taking glucocorticoids to treat pulmonary sarcoidosis. Patients were randomly assigned to be in one of two treatment groups: RCI or placebo. In the first 24 weeks of the study, 27 patients were injected with RCI twice weekly, while 28 patients were injected with an inactive substance (placebo). Forty-seven patients continued into an optional phase of the study for an additional 24 weeks in which all patients received RCI twice weekly. A sarcoidosis treatment score and assessments of lung health, general health, and fatigue were used to determine whether RCI was effective. These assessments showed greater improvements with RCI compared to placebo. Patients who switched from placebo to RCI showed similar improvements to those who remained on RCI throughout the entire study. Patients receiving RCI were able to discontinue their use of glucocorticoids more quickly than those taking placebo, thus helping them to avoid the harmful side effects of the glucocorticoids. Side effects for RCI were mostly mild or moderate, and no new or unexpected safety concerns for RCI were seen throughout the study.

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.

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.

Effects of Subcutaneous Repository Corticotropin Gel Injection on Regulatory T Cell Population in Noninfectious Retinal Vasculitis.

AIM: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis. PATIENTS AND METHODS: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study. RESULTS: Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found. CONCLUSION: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.

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.

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.

A Narrative Review of Repository Corticotropin Injection for the Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems. The most prevalent manifestations include constitutional symptoms, arthritis, and rash. An SLE flare is defined as a measurable increase in disease activity that may prompt a change in treatment. According to the European Alliance of Associations for Rheumatology guidance, SLE treatments should be aimed at reducing disease activity and flares, as well as preventing organ damage. Standard-of-care treatment of SLE includes glucocorticoids, but their long-term use is associated with damage accrual. Repository corticotropin injection (RCI; Acthar® Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides that has anti-inflammatory and immunomodulatory effects beyond its steroidogenic effect, and has been US Food and Drug Administration-approved for the treatment of SLE flares and as a maintenance therapy. This review summarizes data from three clinical trials that evaluated the efficacy and safety of RCI in the treatment of patients with moderate-severe refractory SLE. These clinical trials confirmed that RCI improved global disease activity scores and some SLE clinical manifestations. Analysis of pooled data from these trials showed that RCI treatment significantly improved the British Isles Lupus Assessment Group 2004 (BILAG-2004) index scores after 8 weeks of treatment, and tender and swollen joint counts after 4 weeks. These clinical trials demonstrated an acceptable safety profile with few serious adverse events reported. The distinct mechanisms of action from standard-of-care therapies and the favorable safety and good efficacy profiles support the use of RCI as therapy for patients with refractory SLE.

Results from a Prospective, Open-Label, Phase 4 Pilot Study of Repository Corticotropin Injection for Moderate and Severe Dry Eye Disease.

INTRODUCTION: There is a substantial unmet need for effective therapies to treat patients with refractory dry eye disease (DED). The goal of this open-label pilot study was to investigate the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel; Mallinckrodt Pharmaceuticals) in subjects with DED, most of whom did not experience adequate response to standard-of-care therapies. METHODS: Adults with moderate or severe-acute DED received 80 U of subcutaneous RCI twice weekly for 12 weeks. Primary efficacy outcomes were improvements in corneal fluorescein staining of superficial punctate keratitis (SPK) lesions and Symptom Assessment in Dry Eye (SANDE) scores. Secondary outcomes included changes in Schirmer's test scores, conjunctival lissamine green staining, erythema, intraocular pressure (IOP), and best corrected visual acuity (BCVA). Adverse events (AEs) were assessed continuously throughout the study. RESULTS: Fifteen subjects received at least 1 dose of RCI, and 12 subjects completed the study. Compared to baseline (day 1), significantly fewer fluorescein-stained SPK lesions were detected at day 14 (p = 0.0250) and day 84 (p = 0.0240) after RCI treatment. Mean SANDE scores progressively declined from 62.0 at baseline to 46.9 at day 84. Erythema (p = 0.0046), conjunctival lissamine green staining of SPK lesions (p = 0.0317), and IOP (p = 0.0052) were all significantly improved after 12 weeks of RCI therapy. Schirmer's test scores and BCVA showed no significant changes throughout the study. No ocular AEs or deaths occurred, and no new safety signals were identified for RCI. CONCLUSIONS: These results suggest that RCI may be a safe and effective treatment for moderate and severe DED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03287635.

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.

Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis: A Narrative Review.

Although corticosteroids are the standard first-line therapy for pulmonary sarcoidosis, long-term and high-dose use of these drugs are associated with increased risk of adverse events and high healthcare utilization costs. Treatment guidelines for pulmonary sarcoidosis indicate that off-label immunomodulators and biologics may be warranted for severe disease. Repository corticotropin injection (RCI, Acthar® Gel), a complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides, is one of only two therapies approved by the US Food and Drug Administration for symptomatic pulmonary sarcoidosis and is recommended by current European Respiratory Society treatment guidelines for use on a case-by-case basis. With its unique anti-inflammatory and immunomodulatory mechanism of action through activation of melanocortin receptors in various cell types, RCI has demonstrated steroid-sparing properties. RCI has a long history of use in autoimmune and inflammatory disorders, with proven safety and efficacy for pulmonary sarcoidosis. In this narrative review, we present the clinical evidence for the safety and efficacy of RCI in the treatment of pulmonary sarcoidosis, identify where RCI falls within the current treatment guidelines, and describe the unique mechanism of action of RCI for promoting anti-inflammatory and immunomodulatory effects.

Post Hoc Analysis of Predictors of Clinical Response to Repository Corticotropin Injection in Persistently Active Rheumatoid Arthritis.

INTRODUCTION: A phase IV clinical trial confirmed the safety and efficacy of repository corticotropin injection (RCI, Acthar® Gel) in patients with refractory rheumatoid arthritis (RA) that was nonresponsive to standard-of-care therapies. The objective of this post hoc analysis was to identify baseline demographics and clinical characteristics that may be predictors of response to RCI. METHODS: The phase IV trial was a two-part, randomized, placebo-controlled withdrawal study. Post hoc analysis was conducted with the open-label portion of the trial data, in which all 258 subjects received RCI (80 U) twice weekly for 12 weeks. Responders were subjects who achieved low disease activity (LDA) by a Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) of < 3.2 at week 12. Responders were compared with nonresponders by assessing the proportion of subjects in each group for demographics and clinical characteristics, including weight, disease duration, medical history including osteoarthritis and unrelated joint conditions, hemoglobin A1c, C-reactive protein, ESR, DAS28-ESR, Clinical Disease Activity Index (CDAI), depression, anxiety, tender joint count (TJC), and swollen joint count (SJC). Bivariate analysis followed by multiple logistic regression analysis were conducted to identify significant baseline predictors for the outcome of achieving LDA by week 12. RESULTS: Bivariate analysis showed that RCI responders had significantly lower baseline TJC (p = 0.0310), SJC (p = 0.0018), ESR (p = 0.0487), and CDAI (p = 0.0112) and shorter RA disease duration (p = 0.0446). Subjects were less likely to achieve LDA if they had osteoarthritis (p < 0.0001), other joint-related conditions unrelated to RA (p < 0.0001), anemia (p = 0.0132), depression (p = 0.0006), or prior or concomitant use of targeted-synthetic or biologic disease-modifying antirheumatic drugs (p < 0.0001). Multiple logistic regression analysis revealed that, of the above, only ongoing osteoarthritis (p = 0.0272) or other joint-related conditions (p = 0.0193) were significant negative predictors of RCI response. CONCLUSIONS: These results identify specific patient characteristics that may be considered predictors of positive or negative clinical response to RCI.

Results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection for multiple sclerosis relapse that did not adequately respond to corticosteroids.

INTRODUCTION: About 20%-35% of multiple sclerosis (MS) patients fail to respond to high-dose corticosteroids during a relapse. Repository corticotropin injection (RCI, Acthar® Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and pituitary peptides that has anti-inflammatory and immunomodulatory effects. AIMS: The study objective was to determine the efficacy and safety of RCI in patients with MS relapse that inadequately responded to corticosteroids. This was a multicenter, double-blind, placebo-controlled study. Nonresponders to high-dose corticosteroids were randomized to receive RCI (80 U) or placebo daily for 14 days. Assessments included improvements on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Clinical Global Impression of Improvement (CGI-I), and adverse events (AEs). RESULTS: Eighteen patients received RCI, and 17 received placebo. A greater proportion of EDSS responders was observed in the RCI group at Day 7, 21, and 42 compared with the placebo group. Qualitative CGI-I showed that more patients receiving RCI were much improved or very much improved than with placebo. No meaningful differences were observed between treatment groups for MSIS-29. No serious AEs or deaths were reported. CONCLUSION: RCI is safe and effective for MS relapse patients who do not respond to high-dose corticosteroids.

Repository Corticotropin in Treating de novo C3 Glomerulonephritis after Transplantation.

Introduction: De novo C3 glomerulonephritis (C3GN) after transplant is uncommon. Although eculizumab has been used successfully in several cases, the response is heterogeneous, and treatment strategies remain undefined. The use of repository corticotropin in C3GN has not been described in the literature. Case Report: A 48-year-old African American male with kidney transplantation secondary to presumed diabetic nephropathy presented 6 years after transplant with lower extremity edema and nephrotic range proteinuria. His urine protein to creatinine ratio (UPCR) was 8.2 g/g. Renal allograft biopsy confirmed the diagnosis of C3GN. He was treated with eculizumab (Solaris®) 900 mg IV once weekly for 4 weeks and repository corticotropin (H.P. Acthar® gel) 80 units SQ twice weekly for 6 months with a near-complete resolution of proteinuria within 3 months of the treatment. The patient presented again 6 months after completing the therapy with a recurrence of proteinuria, which peaked at 11.6 g/g of UPCR. Repeat kidney allograft biopsy was consistent with C3GN. He was started on repository corticotropin 80 units SQ twice weekly, which resulted in a reduction of proteinuria to >50% within 2 months of therapy. When eculizumab 900 mg IV weekly for 4 weeks was added with repository corticotropin, the proteinuria resolved within 10 weeks of treatment. The patient was maintained on monotherapy of repository corticotropin and has been in complete remission of proteinuria for more than a year until his last follow-up. Conclusion: This is the first case report describing the role of repository corticotropin as an effective therapy in reducing proteinuria and maintaining patients with C3GN in proteinuria remission.

Post Hoc Analysis of the Correlation Between Patient-Reported Outcomes and Clinical Response to Repository Corticotropin Injection for Persistently Active Rheumatoid Arthritis.

PURPOSE: Approximately 6% of patients with rheumatoid arthritis (RA) in the USA have refractory disease that is resistant to standard-of-care therapies. A recent phase IV clinical trial affirmed the safety and efficacy of repository corticotropin injection (RCI; Acthar® Gel) for refractory RA. This post hoc analysis of the clinical trial data assessed whether changes in clinical measures correlated with patient-reported outcome (PRO) improvements. METHODS: Data were assessed from the trial's open-label period when patients received RCI (80 U) twice weekly for 12 weeks. Clinical assessments included hemoglobin A1c, C-reactive protein, erythrocyte sedimentation rate (ESR), total joint count (TJC), swollen joint count (SJC), Disease Activity Score with 28 joint count and ESR (DAS28-ESR), and Clinical Disease Activity Index (CDAI). PROs included pain (Visual Analog Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and activity impairment (Work Productivity and Activity Impairment [WPAI] questionnaire). Patients grouped by minimal clinically important difference (MCID) improvement vs no improvement in PROs were compared with clinical measures at week 12. Correlations were determined by multivariable linear regression analysis and standardized coefficient estimates. RESULTS: RCI responders, defined as patients with DAS28-ESR < 3.2 at week 12, reported significantly greater PRO improvements for pain, disability, fatigue, activity impairment, current work impairment, and overall work impairment than nonresponders. Patients with MCID improvements in all PROs showed significantly greater decreases in mean values for TJC, DAS28-ESR, and CDAI, whereas those with pain, fatigue, and disability improvements had significantly greater SJC and ESR reductions. Multivariable linear regression analysis determined that improvement from baseline in all PROs correlated with significant decreases in TJC, DAS28-ESR, and CDAI. ESR reduction significantly correlated with improvements in pain and disability, but not fatigue or WPAI. CONCLUSIONS: These results confirm that clinical responses to RCI were directly correlated with patient perception of improvement.