Switching From Immediate-Release to Delayed-Release Prednisone in Moderate to Severe Rheumatoid Arthritis: A Practice-Based Clinical Study

Abstract

Introduction: Rheumatoid arthritis (RA) produces debilitating morning stiffness. Exogenous glucocorticoids can help with these symptoms when timed appropriately. Bedtime dosing of delayed-release prednisone (DR-prednisone) matches the rise of inflammatory cytokines before awakening and can improve stiffness and other RA symptoms. A prospective open-label study was conducted in patients currently on stable doses of immediate-release prednisone (IR-prednisone) who were switched to DR-prednisone to analyze the incremental benefit of better timed and lower dose glucocorticoid therapy.

Methods: Twelve US sites enrolled patients with moderate-severe RA into a 12-week prospective study. Patients were switched from IR- to DR-prednisone while maintaining other existing background therapies. Change from baseline in morning stiffness severity, morning stiffness duration, swollen and tender joint counts (S-TJC), 28 joint disease activity score (DAS28), and patient/physician global assessment (PGA/PhGA), among others, were measured. Post-hoc analyses were performed on those completing 10 weeks of treatment and those with >60 min of morning stiffness at baseline.

Results: Fifty-six patients had at least one follow-up visit and were similar in demographics to previous controlled trials with DR-prednisone with regard to baseline age and DAS28-CRP but had lower morning stiffness and RA duration. DR-prednisone produced a trend toward lower morning stiffness severity and duration with a reduction in daily prednisone dose of almost 1 mg. Patients treated with DR-prednisone for ≥10 weeks demonstrated significant reductions in morning stiffness duration, SJC, TJC, DAS28-CRP, and PhGA (all p ≤ 0.04). Patients treated for ≥10 weeks with >60 min of baseline morning stiffness produced similar results in these measures as well as a 21% reduction in morning stiffness severity (p = 0.02).

Conclusion: Patients switched to DR-prednisone from IR-prednisone in this practice-based study maintained or improved their outcomes across a variety of domains, and results were comparable to previous controlled trials in which patients completed at least 10 weeks of treatment.

Funding: Horizon Pharma USA, Inc.

Trial registration: ClinicalTrials.gov identifier, NCT02287610.

Keywords: Circadian; Glucocorticoids; Morning stiffness; Outcome assessment; Prednisone; Rheumatoid arthritis.

Figures

Fig. 1

Patient disposition. Superscript letter denotes participants who never received the drug who were also categorized as patient choice (2) or lost to follow-up (1). MS morning stiffness

Fig. 2

SJC28 (a), RAPID3 (b), PhGA of disease activity (c), and DAS28-CRP (d) for patients on DR-prednisone with follow-up. Data are summarized as the mean (standard deviation). DAS28-CRP disease activity score in 28 joints by C-reactive protein, PhGA physician global assessment, RAPID3 routine assessment of patient index data, SJC28 swollen joint count of 28 joints, VAS visual analog scale

Fig. 3

Baseline and last follow-up prednisone dosage for patients on DR-prednisone with a follow-up visit, a subset of patients on DR-prednisone for ≥10 weeks, and a subset of patients on DR-prednisone for ≥10 weeks with >60 min of morning stiffness at baseline. Data are summarized as the mean (SD). MS morning stiffness

Fig. 4

SJC28 (a), morning stiffness duration (b), PhGA of disease activity (c), and DAS28-CRP (d) for patients on DR-prednisone for ≥10 weeks. Data are summarized as the mean (standard deviation). DAS28-CRP disease activity score in 28 joints by C-reactive protein; PhGA physician global assessment; RAPID3 routine assessment of patient index data; SJC28 swollen joint count of 28 joints; VAS visual analog scale

Fig. 5

Morning stiffness severity (a), morning stiffness duration (b), PhGA of disease activity (c), DAS28-CRP (d), SJC28 (e), and RAPID3 (f) for patients on DR-prednisone for ≥10 weeks with >60 min of morning stiffness at baseline. Data are summarized as the mean (standard deviation). DAS28-CRP disease activity score in 28 joints by C-reactive protein; PhGA physician global assessment; RAPID3 routine assessment of patient index data; SJC28 swollen joint count of 28 joints; VAS visual analog scale