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Repository corticotropin injection (H.P. Acthar gel) for the treatment of sarcoidosis-induced hypercalciuria and vitamin D dysregulation: a pilot, open label study.

ABSTRACT: Background: Vitamin D dysregulation may occur in sarcoidosis patients and result in hypercalciuria, hypercalcemia, nephrolithiasis, and renal impairment. We performed an open label pilot study of highly purified (H.P.) Acthar® Gel (repository corticotropin injection) (RCI) on patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria. Methods: Nine patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria on stable maintenance anti-sarcoidosis therapy received 80 units of RCI subcutaneously twice weekly for 12 weeks. 24-hour urinary calcium excretion was measured at baseline and at 12 weeks. Other parameters measured over 16 weeks (including 4 weeks post the last RCI dose) included the following serum values: calcium, 25-OH vitamin D, 1,25- diOH vitamin D and serum parathyroid hormone (PTH). In addition, the Sarcoidosis Health Questionnaire (SHQ) and Short Form-36 (SF-36) as well as a urinary symptom score were measured in all subjects. Results: There was no significant change in the 24-hour urinary calcium excretion over 12 weeks of the study. However, there was evidence that RCI improved sarcoidosis-induced vitamin D dysregulation in that the serum 1,25- diOH vitamin D level significantly declined over 12 weeks. There was also improvement in most of the domains of the quality of life measures, although only a few of them reached statistical significance. There was also a trend toward improvement in urinary symptoms over the study period. The was evidence of the development corticosteroid side effects in the cohort, in that weight significantly increased over the study period. Conclusions: In this small pilot open label trial, 12 weeks of RCI did not significantly improve sarcoidosis-induced hypercalciuria. However, some statistically significant changes in serum vitamin D and PTH levels were demonstrated that were consistent with some amelioration of sarcoidosis-induced vitamin D dysregulation. Several corticosteroid-related side effects were demonstrated in this cohort. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 192-197).

SUBMITTER: Judson MA

PROVIDER: S-EPMC7170160 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Repository corticotropin injection (H.P. Acthar gel) for the treatment of sarcoidosis-induced hypercalciuria and vitamin D dysregulation: a pilot, open label study.

Judson Marc A MA Modi Aakash A Ilyas Furqan F Yucel Recai R

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG 20180428 3

<i>Background:</i> Vitamin D dysregulation may occur in sarcoidosis patients and result in hypercalciuria, hypercalcemia, nephrolithiasis, and renal impairment. We performed an open label pilot study of highly purified (H.P.) Acthar® Gel (repository corticotropin injection) (RCI) on patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria. <i>Methods:</i> Nine patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria on stable maintenance anti-sarcoidosis t ...[more]

PMID: 32476902

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Project description:Background and Purpose: Effective relapse treatment is critical for minimizing disability in patients with multiple sclerosis (MS). Repository corticotropin injection (RCI; Acthar® Gel) has demonstrated efficacy for the treatment of MS exacerbations. However, there is limited real-world evidence available regarding the relationship between the use of RCI for MS relapses and patient demographics, disease characteristics, and dosing regimens. In this multicenter, prospective, observational registry, patients receiving RCI for acute MS relapse were characterized, and recovery and safety outcomes were described. Methods: Patients were invited by their treating clinician to participate in the registry during a routine care visit. The decision to initiate RCI occurred before determination of study eligibility. All treatment decisions were made at the discretion of the patient's health care provider and were not mandated by the study design or protocol. Each enrolled patient was followed for up to 24 Months or until the date of study termination. The primary endpoint was the change from baseline in MS Impact Scale Version 1 (MSIS-29v1) physical subscale scores at Month 2. Additional assessments included the MSIS-29v1 psychological subscale, Expanded Disability Status Scale (EDSS), Clinical Global Impression of Improvement (CGI-I), Work Productivity and Activity Impairment Questionnaire: MS (WPAI:MS), and Health Resource Utilization (HRU) questionnaire. Results: Of 145 patients enrolled, 82 (56.6%) completed 24 Months of follow-up. Mean MSIS-29v1 physical subscale scores improved at 2 Months (-8.0; P = 0.0002) and 6 Months (-9.6; P < 0.0001). Mean MSIS-29v1 psychological subscale scores also improved at 2 Months (-7.9; P = 0.0040) and 6 Months (-9.9; P = 0.0012). Mean EDSS scores improved at 2 Months (-0.4; P < 0.0001) and 6 Months (-0.5; P < 0.0001). CGI-I scores indicated improvement in 63.4% of 71 patients at 2 Months and 61.4% of 57 patients at 6 Months (both P < 0.0001). Improvements on the WPAI:MS activity impairment domain (P < 0.001) and reductions in outpatient, specialist, and emergency department visits were observed at 2 and 6 Months. A total of 35 (28.0%) patients reported 83 adverse events; 11 (8.8%) patients reported 16 serious adverse events. Conclusions: This observational study found significant improvements in MS assessment scores after RCI treatment and supports the efficacy and tolerability of RCI for MS relapse. Clinical Trial Registration: This trial is registered on ClinicalTrials.gov with the identifier NCT02633033.

Project description:IntroductionNoninfectious keratitis is a painful corneal inflammation treated with topical cyclosporine and other immunosuppressants. Additional treatment options are needed for keratitis that does not improve with standard therapies. Repository corticotropin injection (RCI; Acthar® Gel) is approved to treat severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, including keratitis. This phase 4, multicenter, open-label study assessed the efficacy and safety of RCI for refractory severe noninfectious keratitis.MethodsPatients were ≥ 18 years old with persistent severe keratitis despite treatment with topical immunosuppressants. Patients received 80 U of RCI subcutaneously twice weekly for 12 weeks followed by a 4-week taper. Assessments included all domains of the Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire, Ocular Discomfort and 4-Symptom Questionnaire, and Visual Analog Scale (VAS). Corneal fluorescein and conjunctival lissamine green staining, Conjunctival Redness Scale, tear production (Schirmer's test), visual acuity, slit lamp examination, and intraocular pressure were also assessed. Safety was evaluated via treatment-emergent adverse events. Analyses were performed using the modified intent-to-treat (mITT) population (patients who received ≥ 1 dose of RCI and contributed any post-baseline efficacy data).ResultsIn the mITT population (N = 35), 50.0% (95% confidence interval, 33.2% to 66.8%) of patients experienced clinically important improvements in the symptom bother domain of the IDEEL Questionnaire at week 12 of RCI therapy. All domains of the IDEEL and the Ocular Discomfort and 4-Symptom Questionnaire showed improvements at week 12 of RCI treatment. The most pronounced improvements in the VAS at week 12 were for eye dryness and eye discomfort. Corneal staining, conjunctival staining, conjunctival redness, and tear production showed early improvements that were sustained through week 12. No new safety signals for RCI were identified.ConclusionsRCI is safe and effective for refractory severe noninfectious keratitis that has not improved with other approved therapies.Trial registration numberClinicalTrials.gov NCT04169061.

Project description:Objective:SLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid use. Methods:Efficacy will be evaluated using the SLE Responder Index-4 (SRI-4), SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) and Physician's Global Assessment (PGA). The primary efficacy endpoint will be the proportion of SRI-4 responders at week 16. Secondary and exploratory endpoints will include changes in disease activity scores over time, prednisone dose and biomarkers of inflammation and bone turnover. The safety and tolerability profile of RCI will also be evaluated through adverse event profiles, physical examination, clinical laboratory tests and serum cortisol levels. Results:Target enrolment for this global study is 270 patients, and as of 15 November 2019, the modified intent-to-treat population included 169 patients. The study cohort had 91.7% women, had a mean age of 39.7 years, mean SLEDAI-2K total score of 9.9, mean BILAG-2004 total score of 18.1, mean PGA of 59.7 and mean prednisone or equivalent daily dose of 11.1?mg. A total of 79.3% and 64.5% of patients were receiving concomitant antimalarial or immunosuppressive therapy, respectively. Conclusions:Data from this study will provide valuable insights into the therapeutic role of RCI in refractory SLE, as well as important information regarding its safety profile.

Project description:BACKGROUND:Repository corticotropin injection (RCI) has regulatory approval for many indications, including symptomatic sarcoidosis. This large case series of patients with advanced symptomatic sarcoidosis treated with RCI describes patient characteristics, RCI utilization patterns, concomitant therapies, and physicians' assessments of treatment response. METHODS:Patients ?18?years with symptomatic sarcoidosis, treated with RCI in the previous 36?months, who had completed a course of RCI or received RCI for ?6?months at the time of data collection were included. RESULTS:The study included 302 patients (mean age, 51?years; 52%, women) with a mean 4.8 years since initial diagnosis of sarcoidosis. Most patients (76%) had extrapulmonary involvement, primarily in the skin (28%), joints (25%), heart (22%), and eyes (22%); 34% had multiple (?2) organ involvement. The mean duration of RCI treatment was 32.5?weeks, with 61.6% of patients continuing RCI therapy for ?6?months. The RCI utilization pattern indicated an individualized approach to therapy, with a higher starting dose associated with a shorter duration of therapy compared with a lower starting dose. The percentage of patients who used corticosteroids decreased from 61.3% during the 3?months before initiation of RCI to 12.9% 3?months after RCI therapy; the mean daily dose of corticosteroid decreased from 18.2?mg to 9.9?mg. The proportion of patients given <10?mg/day of prednisone increased from 21% before RCI use to 47% 3?months after RCI use. According to physicians' assessments of change in patients' health status after RCI therapy, overall status improved in 95% of patients, overall symptoms in 73%, lung function in 38%, and inflammation in 33%. CONCLUSIONS:The findings suggest that RCI is a viable treatment option for patients with advanced symptomatic sarcoidosis and provide insights on patient characteristics and practice patterns to help clinicians determine appropriate use. The reviews of this paper are available via the supplemental material section.

Project description:IntroductionWe conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids.MethodsAdults with active SLE and moderate to severe rash and/or arthritis were enrolled in the primary study. Patients had active SLE despite treatment with stable glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs and/or immunosuppressants. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day for 4 weeks and then twice weekly through week 24. Blood samples were analyzed for serum cytokines and complement proteins using enzyme-linked immunosorbent or Luminex assays and for circulating leukocytes using flow cytometry. Biomarker levels were reported as percentages of the baseline and were further evaluated in subgroups stratified by baseline SLE Disease Activity Index-2000 (SLEDAI-2K) scores (< 10 vs. ≥ 10), baseline anti-double-stranded DNA levels (< 15 IU/mL vs. ≥ 15 IU/mL), and BILAG-based Combined Lupus Assessment (BICLA) responses at week 20 and 24.ResultsRCI treatment resulted in reduced levels of B cell-activating factor and interleukin-6 cytokines in all subgroups compared with placebo. RCI treatment also resulted in lower levels of CD19+ B cells and CD19+IgD-CD27-CD95+ atypical activated memory B cells than did placebo in the higher baseline disease activity subgroups and in BICLA non-responders. Furthermore, RCI treatment led to greater increases in complement component (C)3 and C4 levels than did placebo in the higher baseline disease activity subgroups and in BICLA responders.ConclusionsRCI may reduce inflammation through B cell immunomodulation in patients with persistently active SLE, particularly in those with higher disease activity.Trial registrationClinicalTrials.gov identifier NCT02953821.

Project description:IntroductionWe assessed patient-reported outcomes from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids.MethodsThe trial enrolled adults with active SLE and moderate-to-severe rash and/or arthritis despite use of stable glucocorticoids (7.5 mg/day to 30 mg/day prednisone equivalent), antimalarials, and nonsteroidal anti-inflammatory drugs for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day through week 4, then twice weekly through week 24. Primary analyses evaluated the change from baseline to week 24 in the Lupus Quality of Life (QoL) and Work Productivity and Activity Impairment (WPAI)-Lupus questionnaires. Post hoc analyses stratified results by baseline disease activity (SLE Disease Activity Index-2000 [SLEDAI-2K] < 10 or ≥ 10; Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI]-Activity < 11 or ≥ 11; and British Isles Lupus Assessment Group [BILAG]-2004 < 20 or ≥ 20) and by BILAG-based Combined Lupus Assessment (BICLA) response at weeks 20 and 24.ResultsRCI treatment resulted in greater improvement in the LupusQoL pain domain at week 16 and planning domain at week 24 compared with placebo. Post hoc analyses demonstrated greater improvements with RCI in the pain, planning, and fatigue domains than with placebo at multiple time points in patients with higher disease activity by baseline SLEDAI-2K ≥ 10, CLASI-Activity ≥ 11, and BILAG-2004 ≥ 20 and/or in BICLA responders. Compared with placebo, RCI also resulted in greater improvements in percentage work time missed at week 24 in patients with baseline CLASI-Activity < 11 and in percentage impairment while working at week 16 in BICLA responders.ConclusionsRCI may improve QoL and work productivity in patients who have persistently active SLE despite treatment with standard SLE therapy.Trial registrationClinicalTrials.gov identifier NCT02953821.

Project description:IntroductionLong-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.MethodsIn 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.ResultsFifty-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.ConclusionsRCI 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 registrationClinicalTrials.gov identifier: NCT03320070.

Dataset Information

Repository corticotropin injection (H.P. Acthar gel) for the treatment of sarcoidosis-induced hypercalciuria and vitamin D dysregulation: a pilot, open label study.

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Repository corticotropin injection (H.P. Acthar gel) for the treatment of sarcoidosis-induced hypercalciuria and vitamin D dysregulation: a pilot, open label study.

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