Repository corticotropin injection in patients with persistently active SLE requiring corticosteroids: post hoc analysis of results from a two-part, 52-week pilot study

Furie, Richard; Mitrane, Margaret; Zhao, Enxu; Becker, Patrice M.

doi:10.1136/lupus-2017-000240

Cited by 14 publications

(32 citation statements)

References 22 publications

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“…The effectiveness of RCI for the treatment of SLE has been demonstrated in previous clinical studies [ 10 – 12 ]. Findings from a pilot study [ 11 ] and subsequent post hoc analyses [ 12 ] suggested that RCI is safe and may be effective for treating patients who have persistently active SLE despite treatment with moderate-dose glucocorticoids. These results provided the impetus for further evaluation of RCI in a larger study of SLE.…”

Section: Introductionmentioning

confidence: 97%

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

et al. 2020

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Introduction: We assessed the efficacy and safety of repository corticotropin injection (RCI; Acthar Ò Gel) for persistently active systemic lupus erythematosus (SLE) despite use of moderate-dose glucocorticoids. Methods: This multicenter, double-blind, randomized, placebo-controlled study enrolled patients C 18 years with active SLE and moderate to severe rash and/or arthritis despite stable glucocorticoid doses (7.5-30 mg/day prednisone equivalent) and antimalarials for C 4 weeks and/or immunosuppressants for C 8 weeks before screening. Stable glucocorticoid doses were required through week 16 with optional taper from weeks 16 to 24. Patients were randomized (1:1) to 80 U RCI subcutaneously or placebo every other day to week 4, then twice weekly to week 24. Endpoints included the proportion of SLE Responder Index (SRI)-4 responders at week 16; changes from baseline to week 16 in 28 Swollen Joint Count/ Tender Joint Count (28 SJC/TJC) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity score; and changes from baseline to week 24 in inflammatory cytokines. Safety was assessed by adverse events. Results: In the modified intention-to-treat population (RCI, n = 84; placebo, n = 85), the proportion of SRI-4 responders at week 16 was not significantly different between groups (RCI, 47.6%; placebo, 43.5%; OR [95% CI] 1.2 [0.6 to 2.2]; p = 0.5762). RCI treatment resulted in a reduction from baseline to week 16 in 28 SJC/TJC and CLASI-Activity score and from baseline to week 8 in a proliferation-inducing ligand cytokine. Post hoc analyses demonstrated a greater proportion of BILAG-based Combined Lupus Assessment responders for RCI than placebo at weeks 4, 12, and 20 and greater SRI-4 response in RCI-treated patients with baseline SLE Disease Activity Index-2000 C 10 and CLASI-Activity C 11. No new safety signals were identified. Conclusions: Despite failure to achieve the primary endpoint, these results support the utility of RCI for treating persistently active SLE. Trial Registration: ClinicalTrials.gov identifier NCT02953821. Digital Features This article is published with digital features to facilitate understanding of the article. To view digital features for this article go to

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Section: Introductionmentioning

confidence: 97%

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

et al. 2020

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“…16 While this exploratory study found that numerical differences were not statistically significant in the primary endpoint, a composite responder index, secondary endpoints and post hoc analyses linked RCI treatment to sustained improvements in SLE signs and symptoms and a tolerable safety profile. 16,17 These results supported the design of a wellpowered, ongoing, randomized, double-blind placebocontrolled study (NCT02953821) to evaluate 24 weeks of treatment with RCI in patients with persistently active SLE despite treatment with moderate-dose corticosteroids.…”

Section: Safetymentioning

confidence: 67%

“…12 RCI has been used successfully to treat patients with SLE exacerbations not controlled by conventional treatments. [13][14][15][16][17] In the United States, DM has a prevalence of 1 to 6 per 100,000 persons, and PM ranges from the largest fraction with approximately 10 per 100,000 persons in the United States down to the rarest condition that should only be diagnosed by exclusion. 18 Glucocorticoids are used for first-line treatment of patients with DM/PM, followed by (or in conjunction with) immunosuppressive maintenance; in case of intolerance or insufficient response, oral cyclosporine or intravenous immunoglobulin G may be used and, upon relapse or interstitial lung disease, rituximab or cyclophosphamide may be considered.…”

Section: Introductionmentioning

confidence: 99%

<p>Treatment with Repository Corticotropin Injection in Patients with Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Dermatomyositis/Polymyositis</p>

Mahler¹,

Turner²,

Eaddy³

et al. 2020

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Purpose: Repository corticotropin injection (RCI) is indicated for a number of autoimmunemediated diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and dermatomyositis (DM)/polymyositis (PM). To better understand the practice patterns and outcomes of RCI in patients with RA, SLE, or DM/PM, we conducted a retrospective medical record analysis. Patients and Methods: Participating providers selected deidentified medical records of patients meeting the inclusion criteria (age ≥18 years; physician-reported diagnosis of RA, SLE, or DM/PM; initiation of treatment with RCI between 1/1/2011 and 2/15/2016; ≥3 inoffice visits with same site/provider). Collected data spanned 12 months before and after the first prescription date for RCI. Analyses included patient demographics and clinical history, RCI treatment patterns, and physician's impression of change. Results: Data from 54 patients with RA, 30 patients with SLE, and 8 patients with DM/ PM were analyzed. The most frequently reported reasons for initiating RCI were lack of efficacy with prior treatment, acute exacerbation of disease, and use as add-on to ongoing therapy. The most common initial RCI dosing, 80 U twice weekly, was used for 84% of patients with RA, 75% with SLE, and 86% with DM/PM. The mean duration of treatment was 4.8, 6.5, and 6.8 months for RA, SLE, and DM/PM, respectively. Among the 57 patients with data on physician's impression of change with RCI, 78.1% of patients with RA, 94.7% with SLE, and 66.7% with DM/PM had a rating of "improved," and the mean time to best impression of change was 3.4, 4.3, and 3.4 months for RA, SLE, and DM/PM, respectively. Conclusion: This study reports the real-world patient profile, use patterns, and outcomes of patients who used RCI for the treatment of RA, SLE, and DM/PM. These data can inform appropriate use and clinical expectations when using RCI.

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“…In a separate post hoc analysis of these pilot study data, treatment with RCI demonstrated sustained improvements in disease activity over the 52-week study period. 23 These results provide a rationale for further clinical investigation of RCI for the treatment of persistently active SLE in larger studies evaluating validated response measures, such as the SRI-4. Here, we describe the design and baseline patient characteristics of this multicentre, randomised, double-blind, placebocontrolled trial.…”

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confidence: 75%

Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial

et al. 2020

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ObjectiveSLE 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.MethodsEfficacy 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.ResultsTarget 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.ConclusionsData 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.

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Repository corticotropin injection in patients with persistently active SLE requiring corticosteroids: post hoc analysis of results from a two-part, 52-week pilot study

Cited by 14 publications

References 22 publications

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

<p>Treatment with Repository Corticotropin Injection in Patients with Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Dermatomyositis/Polymyositis</p>

Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial

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