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

Abstract

Introduction: We 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.

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 ≥ 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.

Results: RCI 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.

Conclusions: RCI may improve QoL and work productivity in patients who have persistently active SLE despite treatment with standard SLE therapy.

Trial registration: ClinicalTrials.gov identifier NCT02953821.

Keywords: Acthar Gel; Autoimmune disease; Glucocorticoid; Patient-reported outcomes; Repository corticotropin injection; Systemic lupus erythematosus.

Figures

Fig. 1

Change from baseline in the LupusQoL pain domain by baseline SLEDAI-2K (a), baseline CLASI-Activity (b), baseline BILAG-2004 (c), and BICLA response (d), mITT populationa. aPatients who received ≥ 1 dose of study drug and contributed any postbaseline efficacy data. MCIDs are based on the definitions proposed by McElhone et al. [26]. *p < 0.05 (nominal); **p < 0.01 (nominal) for the LS mean difference using ANCOVA models with the change from baseline as the dependent variable, treatments as the factor, and baseline values of corresponding endpoints as the covariate, with stratification for location (US and outside the US) and baseline prednisone or equivalent glucocorticoid dose (≤ 20 mg/day and > 20 mg/day). ANCOVA analysis of covariance, BICLA British Isles Lupus Assessment Group-based Combined Lupus Assessment, BILAG-2004 British Isles Lupus Assessment Group-2004, CLASI-Activity Cutaneous Lupus Erythematosus Disease Severity Index-Activity, LS least squares, LupusQoL Lupus Quality of Life, MCID minimal clinically important difference, mITT modified intention-to-treat, RCI repository corticotropin injection, SEM standard error of the mean, SLEDAI-2K Systemic Lupus Erythematosus Disease Activity Index-2000

Fig. 2

Change from baseline in the LupusQoL planning domain by baseline CLASI-activity (a), baseline BILAG-2004 (b), and BICLA response (c), mITT populationa. aPatients who received ≥ 1 dose of study drug and contributed any postbaseline efficacy data. MCIDs are based on the definitions proposed by McElhone et al. [26]. *p < 0.05 (nominal); **p < 0.01 (nominal) for the LS mean difference using ANCOVA models with the change from baseline as the dependent variable, treatments as the factor, and baseline values of corresponding endpoints as the covariate, with stratification for location (US and outside the US) and baseline prednisone or equivalent glucocorticoid dose (≤ 20 mg/day and > 20 mg/day). ANCOVA analysis of covariance, BICLA British Isles Lupus Assessment Group-based Combined Lupus Assessment, BILAG-2004 British Isles Lupus Assessment Group-2004, CLASI-Activity Cutaneous Lupus Erythematosus Disease Severity Index-Activity, LS least squares, LupusQoL Lupus Quality of Life, MCID minimal clinically important difference, mITT modified intention-to-treat, RCI repository corticotropin injection, SEM standard error of the mean

Fig. 3

Change from baseline in the LupusQoL fatigue domain by baseline SLEDAI-2K (a) and baseline CLASI-activity (b), mITT populationa. aPatients who received ≥ 1 dose of study drug and contributed any postbaseline efficacy data. MCIDs are based on the definitions proposed by McElhone et al. [26]. *p < 0.05 (nominal) for the LS mean difference using ANCOVA models with the change from baseline as the dependent variable, treatments as the factor, and baseline values of corresponding endpoints as the covariate, with stratification for location (US and outside the US) and baseline prednisone or equivalent glucocorticoid dose (≤ 20 mg/day and > 20 mg/day). ANCOVA analysis of covariance, CLASI-Activity Cutaneous Lupus Erythematosus Disease Severity Index-Activity, LS least squares, LupusQoL Lupus Quality of Life, MCID minimal clinically important difference, mITT modified intention-to-treat, RCI repository corticotropin injection, SEM standard error of the mean, SLEDAI-2K Systemic Lupus Erythematosus Disease Activity Index-2000

Fig. 4

Percentage change from baseline in the WPAI-Lupus percentage impairment while working domain by BICLA response, mITT populationa. aPatients who received ≥ 1 dose of study drug and contributed any postbaseline efficacy data. **p < 0.01 (nominal) for the LS mean difference using ANCOVA models with the change from baseline as the dependent variable, treatments as the factor, and baseline values of corresponding endpoints as the covariate, with stratification for location (US and outside the US) and baseline prednisone or equivalent glucocorticoid dose (≤ 20 mg/day and > 20 mg/day). ANCOVA analysis of covariance, BICLA British Isles Lupus Assessment Group-based Combined Lupus Assessment, LS least squares, mITT modified intention-to-treat, RCI repository corticotropin injection, SEM standard error of the mean, WPAI-Lupus Working Productivity and Activity Impairment-Lupus