Session Information
Date: Sunday, November 8, 2015
Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Melanocortins such as corticotropin and alpha-MSH may modulate steroid-independent immune responses relevant to SLE pathophysiology. We previously reported that repository corticotropin injection (RCI), an FDA approved melanocortin therapeutic, attenuated B cell development, circulating autoantibody titers, and disease activity in a murine SLE model, supporting the efficacy of RCI as a treatment alternative for patients with SLE.
Methods:
This 8 wk double-blind randomized placebo-controlled study assessed clinical efficacy of RCI in patients with persistently active SLE despite moderate dose corticosteroids. The primary objective was to explore the effects of RCI on the Hybrid SLE Disease Activity Index (hSLEDAI), with key secondary objectives to evaluate effects on British Isles Lupus Assessment Group-2004 (BILAG), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), and 28-joint count score. Patients were eligible if they had persistently active SLE (hSLEDAI >2) with arthritis and/or skin involvement and BILAG A or B in mucocutaneous and/ or musculoskeletal systems despite 7.5-30 mg prednisone daily for ≥ 4 wk prior to screening. 38 subjects were randomized to receive SC RCI 80 U every other day (RCI80; n=13) or 40 U daily (RCI40; n=13), or SC Placebo gel (n=12). Study medication was maintained at the assigned regimen for 4 wk, then tapered over 4 wk to 2x/wk administration of the assigned dose. Clinical response was assessed by change from baseline for hSLEDAI (wk 2, 4, 6 & 8), BILAG, CLASI, and Tender & Swollen Joint Count (wk 4 & 8).
Results:
Mean hSLEDAI scores at baseline were 9.8±2.1, 8.7±2.9, 11.3±3.3, and 10.0±3.3 in the Placebo, RCI40, RCI80, and combined RCI groups, respectively (mean ±SD). Baseline BILAG and CLASI scores were similar between groups, though tender swollen joint count was higher in subjects randomized to RCI80 vs RCI40 or Placebo (p≤ 0.05). RCI led to significant improvement in key efficacy endpoints compared with Placebo, including total hSLEDAI and BILAG scores, CLASI Activity, and Tender & Swollen Joint Count. There were no significant differences in the incidence of treatment-emergent adverse events between groups.
|
Activity index change from baseline |
Time |
Placebo LS mean (SE) |
RCI 40U QD LS mean (SE) |
RCI 80U QOD LS mean (SE) |
RCI (combined) LS mean (SE) |
|
hSLEDAI |
4 wk |
-1.2 (0.6) |
-1.2 (0.6) |
-2.1 (0.6) |
-1.6 (0.4) |
|
6 wk |
-1.4 (0.7)
|
-2.9 (0.7)
|
-3.5 (0.7)* *p=0.045 |
-3.2 (0.5)* *p=0.040 |
|
|
8 wk |
-0.8 (0.9) |
-3.7 (0.9)* *p=0.026 |
-3.9 (0.9)* *p=0.020 |
-3.8 (0.6)* *p= 0.008 |
|
|
BILAG |
4 wk |
-4.7 (1.6) |
-5.2 (1.5) |
-7.2 (1.6) |
-6.1 (1.1) |
|
8 wk |
-1.8 (1.5) |
-8.1 (1.4)* *p=0.005 |
-9.3 (1.6)* *p=0.002 |
-8.6 (1.0)* *p=0.001 |
|
|
CLASI Activity |
4 wk |
-0.2 (0.7) |
-2.2 (0.7)* *p=0.051 |
-1.7 (0.7) |
-2.0 (0.5)* *p=0.050 |
|
8 wk |
-0.6 (1.0) |
-3.7 (1.0)* *p=0.030 |
-2.3 (1.1) |
-3.1 (0.7)* *p=0.047 |
|
|
Tender & Swollen Joint Ct |
4 wk |
-2.5 (0.8) |
-2.3 (0.7) |
-3.5 (0.8) |
-2.8 (0.5) |
|
8 wk |
-2.5 (0.5) |
-2.8 (0.5) |
-4.4 (0.6)* *p=0.019 |
-3.5 (0.4) |
Conclusion:
These data demonstrate that RCI reduces disease activity in patients requiring corticosteroids for persistently active SLE, and that improvements occur within 8 wk of treatment initiation. The tolerability, steroid-sparing effects, and impact of RCI on long-term disease control are being further evaluated in an ongoing open-label extension of this study.
To cite this abstract in AMA style:
Furie R, Das M, Li D, Smythe S, Mathura E, Becker P. Repository Corticotropin Injection (H.P. Acthar® Gel) Attenuates Disease Activity in Patients with Persistently Active Systemic Lupus Erythematosus (SLE) Requiring Corticosteroids [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/repository-corticotropin-injection-h-p-acthar-gel-attenuates-disease-activity-in-patients-with-persistently-active-systemic-lupus-erythematosus-sle-requiring-corticosteroids/. Accessed September 23, 2020.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/repository-corticotropin-injection-h-p-acthar-gel-attenuates-disease-activity-in-patients-with-persistently-active-systemic-lupus-erythematosus-sle-requiring-corticosteroids/