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

Askanase, Anca; Zhao, Enxu; Zhu, Jessica; Connolly-Strong, Erin; Furie, Richard

doi:10.1136/lupus-2020-000383

Cited by 5 publications

(7 citation statements)

References 25 publications

(23 reference statements)

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“…This multicenter, randomized, double-blind, parallel-group, placebo-controlled study was conducted across 54 study sites in Argentina, Chile, Mexico, Peru, and the US. The study design has been described in detail previously [ 13 ]. Investigators enrolled adults aged ≥ 18 years with active SLE (≥ 4 of 11 American College of Rheumatology criteria [ 14 ]; SLE Disease Activity Index-2000 [SLEDAI-2K] [ 15 ] score ≥ 6 at screening; and clinical SLEDAI-2K [excluding laboratory results] score ≥ 4 at both screening and randomization) and with moderate to severe rash and/or arthritis by British Isles Lupus Assessment Group-2004 (BILAG-2004) [ 16 ] scores A or B in the mucocutaneous or musculoskeletal domains at both screening and randomization.…”

Section: Methodsmentioning

confidence: 99%

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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: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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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“…Demographics and baseline disease characteristics for patients in each treatment group have been previously described [ 17 , 18 ]. Briefly, the mITT population ( N = 169; RCI, n = 84; placebo, n = 85) was predominantly female (91.7%) with a mean age of 39.7 years and a mean baseline SLEDAI-2K score of 9.9.…”

Section: Resultsmentioning

confidence: 99%

“…Limitations of the primary study have been described previously [ 17 , 18 ]. As a post hoc analysis, this study is inherently subject to subgroup selection bias.…”

Section: Discussionmentioning

confidence: 99%

Patient-Reported Outcomes from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar® Gel) for Persistently Active Systemic Lupus Erythematosus

et al. 2021

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Introduction: We assessed patient-reported outcomes from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar Ò Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids. Methods: The 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 C 4 weeks and/or immunosuppressants for C 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.

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“…The methodology and procedures for the primary study were described in more detail previously [19,21].…”

Section: Methodsmentioning

confidence: 99%

Post Hoc Biomarker Analyses from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar® Gel) for Persistently Active Systemic Lupus Erythematosus

et al. 2021

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Introduction: We conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; ActharÒ Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids. Methods: Adults 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. C 10), baseline anti-double-stranded DNA levels (\ 15 IU/mL vs. C 15 IU/mL), and BILAG-based Combined Lupus Assessment (BICLA) responses at week 20 and 24. Results: RCI 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. Conclusions: RCI may reduce inflammation through B cell immunomodulation in patients with persistently active SLE, particularly in those with higher disease activity. Trial registration: ClinicalTrials.gov identifier NCT02953821.

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

Cited by 5 publications

References 25 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

Patient-Reported Outcomes from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar® Gel) for Persistently Active Systemic Lupus Erythematosus

Post Hoc Biomarker Analyses from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar® Gel) for Persistently Active Systemic Lupus Erythematosus

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