Background Use of oral corticosteroids (CS) in rheumatoid arthritis (RA) remains controversial. While short-term use in early disease or during flares is suggested to reduce inflammation and erosion, side effects and unproven long-term benefit have led to recommendations for their limited use.1
Objectives To assess the effects of different CS doses on adverse event (AE) profiles and radiographic progression of RA patients (pts) treated with certolizumab pegol (CZP).
Methods A post hoc analysis was performed on 982 pts treated with CZP (400mg at weeks [Wks] 0, 2 and 4 followed by 200mg or 400mg every 2 Wks) plus methotrexate (MTX), or placebo (PBO) plus MTX in the RAPID1 trial.2The majority of PBO pts withdrew early. The key outcome was incidence rate of AEs and serious AEs (SAEs) (cases per 100 pt years [pt-yrs]) by Wk52. Radiographic progression (modified Total Sharp Score [mTSS]) was also assessed. Data was stratified by baseline (BL) systemic oral prednisone use (no steroid, ≤5mg/day or >5mg/day). A maximum steroid dose of 10mg/day was allowed in the trial protocol.
Results Baseline characteristics (DAS28[ESR], swollen and tender joint counts) were similar between the two arms and steroid groups. The exception was higher mTSS in the >5mg/day group (median: 27.5) vs no steroid group (19.5) in the PBO arm, possibly related to a trend for higher CRP in the >5mg/day group (median: 23.0mg/L) vs no steroid group (14.0mg/L).There was a clinically relevant trend for higher SAE and serious infections in both arms in the >5mg/day vs no steroid and ≤5mg/day groups (Table). For CZP pts, mean change from baseline (CFB) in mTSS at Wk52 was -0.38, 0.61 and 1.00 for no steroid (n=295), ≤5mg/day (n=197) and >5mg/day (n=225) groups, respectively. Mean CFB in mTSS for PBO was 3.04, 2.41 and 3.00 for the no steroid (n=74), ≤5mg/day (n=38) and >5mg/day (n=63) groups. % mTSS non-progressors in the CZP vs PBO arms for the no steroid, ≤5mg/day and >5mg/day groups were 75.9, 81.7, 74.7 vs 48.6, 60.5, 57.1.
Conclusions Higher doses of CS may be associated with increased rates of SAEs and serious infections. This has important implications for the interpretation of safety data from biologic clinical trials that do not report CS dose. In contrast to the previous hypothesis that CS have structure modifying properties, no incremental benefit in radiographic progression was observed with higher steroid doses.
Smolen JS, et al. Ann Rheum Dis 2010; 69(6):964-75.
Keystone E, et al. Arthritis Rheum 2008; 58(11):3319–29
Disclosure of Interest B. Haraoui: None Declared, B. Combe Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, M. Champsaur Employee of: UCB Pharma, K. Luijtens Employee of: UCB Pharma, E. Keystone Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma
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