Abstract
PURPOSE: Approximately 6% of patients with rheumatoid arthritis (RA) in the USA have refractory disease that is resistant to standard-of-care therapies. A recent phase IV clinical trial affirmed the safety and efficacy of repository corticotropin injection (RCI; Acthar® Gel) for refractory RA. This post hoc analysis of the clinical trial data assessed whether changes in clinical measures correlated with patient-reported outcome (PRO) improvements. METHODS: Data were assessed from the trial's open-label period when patients received RCI (80 U) twice weekly for 12 weeks. Clinical assessments included hemoglobin A1c, C-reactive protein, erythrocyte sedimentation rate (ESR), total joint count (TJC), swollen joint count (SJC), Disease Activity Score with 28 joint count and ESR (DAS28-ESR), and Clinical Disease Activity Index (CDAI). PROs included pain (Visual Analog Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and activity impairment (Work Productivity and Activity Impairment [WPAI] questionnaire). Patients grouped by minimal clinically important difference (MCID) improvement vs no improvement in PROs were compared with clinical measures at week 12. Correlations were determined by multivariable linear regression analysis and standardized coefficient estimates. RESULTS: RCI responders, defined as patients with DAS28-ESR < 3.2 at week 12, reported significantly greater PRO improvements for pain, disability, fatigue, activity impairment, current work impairment, and overall work impairment than nonresponders. Patients with MCID improvements in all PROs showed significantly greater decreases in mean values for TJC, DAS28-ESR, and CDAI, whereas those with pain, fatigue, and disability improvements had significantly greater SJC and ESR reductions. Multivariable linear regression analysis determined that improvement from baseline in all PROs correlated with significant decreases in TJC, DAS28-ESR, and CDAI. ESR reduction significantly correlated with improvements in pain and disability, but not fatigue or WPAI. CONCLUSIONS: These results confirm that clinical responses to RCI were directly correlated with patient perception of improvement.