Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2)

Abstract

ObjectiveTo assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA).MethodsIn this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed.ResultsMR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p<0.001) and ACR50 (22% vs 10%, p<0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p<0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28) (p<0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p<0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%).ConclusionLow-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms.ClinicalTrials.gov, numberNCT00650078

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

“…Rheumatoid arthritis, a systemic inflammatory disease with links to oxidative stress and circadian rhythms, is another disease in which a benefit has been shown when timing treatments with biological rhythms. A slow-release form of prednisone has been developed, so that the rise of proinflammatory cytokines in the morning could be counteracted (23). In cancer, chronotherapeutic treatments have been studied more extensively [reviewed in Ref.…”

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

“…As the length of time between baseline and follow-up measurements was not mandated by the study design, the number of patients and length of time on study may have differed within each measurement and cohort examined. A subset of the endpoints was evaluated in the patients receiving DR-prednisone for C10 weeks and in patients who were receiving DR-prednisone for C10 weeks and had [60 min of morning stiffness at baseline to match that seen in the previously published controlled trials [5,6,8,9].…”

“…IR-prednisone is typically dosed upon awakening after the peak of the inflammatory process in RA. A 12-week, randomized controlled study previously demonstrated that patients treated with concomitant DMARDs and DR-prednisone had a significant reduction in morning stiffness compared with patients treated with DMARD monotherapy [5]. Another 12-week, randomized trial showed that patients treated with DR-prednisone had significantly reduced morning stiffness compared with those treated with IR-prednisone [6], and similar improvements were observed in patients who switched from IR-to DR-prednisone in an open-label extension trial [7,8].…”

Is the Availability of Delayed‐Release Prednisone an Important Clinical Advance?

“…We also know that after giving prednisone (5 mg), serum IL-6 will be diminished (18). It has been shown that the sustained-release prednisone given at night is more effective in controlling morning stiffness than the dose given in the morning (19). Does this approach have a comparable effect limiting bone damage?…”