Table 1.

Clinical trials comparing the efficacy of low-dose GCs (5–10 mg/d) in combination with DMARDs vs DMARDs alone, in patients with early RA (disease duration <1–2 years). Outcome measures are ordered based on the study primary and secondary objectives

Reference	Study design (duration)	Intervention	Sample size (disease duration)	Outcome measure	Results in the GC vs ctrl group
Boers et al24	RCT, MC, DB (80 wks)	• SSZ + MTX + prednisolone (tapered from 60 to 7.5 mg/d in 6 wks) • SSZ alone	N=155 (<2 yrs) • GC arm: 76 • Ctrl arm: 79	• Disease activity and physical function • Radiographic damage	• Rapid improvement, sustained up to wk 28, no longer significant after prednisone withdrawal; at wk 28, higher ACR20 (72% vs 49%, P=0.006) and ACR50 response rate (49% vs 27%, P=0.007) • Significantly slower progression at wk 28, persisting after prednisone withdrawal up to 5 yrs51
Svensson et al25	RCT, MC, OL (2 yrs)	• DMARDs + prednisolone (7.5 mg/d) • DMARDs alone	N=250 (≤1 yr) • GC arm: 119 • Ctrl arm: 131	• Radiographic damage • Disease activity and functional disability and impairment • Bone mineral density	• Significantly less change already at 1 yr, lasting up to 2 yrs. Significantly less newly eroded joints at 1 yr and 2 yrs • Significant improvement already at month 3 by DAS28, HAQ, and SOFI, persisting throughout the study period; significantly higher remission rate at 2 yrs (55.5% vs 32.8%, P=0.0005); significantly lower CRP level at 3–6 months • Similar bone loss
Wassenberg et al26	RCT, MC, DB (2 yrs)	• DMARDs + prednisolone (5 mg/d) • DMARDs + placebo	N=186 (<2 yrs) • GC arm: 80 • Ctrl arm: 86	• Radiographic damage • Clinical and functional outcomes, and remission rate	• Significantly less progression by Ratingen score and SHS already at month 6 and up to month 24; lower % of eroded joints only at 6 months • Trend to higher overall improvement, but without between-group statistical significance
Todoerti et al27	RCT, SC, OL (2 yrs)	• Step-up DMARDs + prednisone (12.5 mg/d for 2 wks, tapered to 6.25 mg/d) • Step-up DMARDs	N=210 (<1 yr) • GC arm: 105 • Ctrl arm: 105	• Clinical remission	• Significantly higher remission rate after 2 months (25.5% vs 8%, P=0.001); significantly higher probability of being in remission within 1 yr (OR: 1.965, 95% CI: 1.214–3.182, P=0.006) and up to 18 months (OR: 4.48, 95% CI: 1.35–14.82, P=0.014)
Bakker et al28	RCT, MC, DB (2 yrs)	• MTX-based tight control strategy + prednisone (10 mg/d) • MTX-based tight control strategy + placebo	N=236 (<1 yr) • GC arm: 117 • Ctrl arm: 119	• Erosive joint damage • Disease activity	• Limited and significantly lower at 2 yrs • More rapid improvement (already at month 3) of DAS28, ESR, VAS pain, and HAQ, yet not sustained over time; higher ACR50 response rate at 1 yr (56% vs 43%, P=0.037) and ACR70 at 2 yrs (38% vs 19%, P=0.002); shorter time to sustained remission (6 vs 11 months, P<0.001); reduced need for additional treatments (22% vs 50% of pts, P<0.001) and lower mean maximum MTX dose (19.7±6.1 vs 23.4±4.5 mg/wk, P<0.001)
Montecucco et al29	RCT, MC, OL (1 yr)	• Step-up MTX + prednisone (6.25 mg/d) • Step-up MTX	N=220 (<1 yr) • GC arm: 110 • Ctrl arm: 110	• Disease activity • Subclinical synovitis	• Significantly higher clinical remission rate at 1 yr (44.8% vs 27.8%, P=0.02); rapid (already at month 2) improvement of pain, DAS28, and number of swollen joints, although not sustained over time; rapid (from month 2) and persistent control of ESR and CRP serum levels • Significantly higher rate of PD negativity (69.8% vs 53.3% of pts, P=0.04)

Abbreviations: ACR20, ≥20% improvement according to the American College of Rheumatology criteria; ACR50, ≥50% improvement according to the ACR criteria; ACR70, ≥70% improvement according to the ACR criteria; CI, confidence interval; CRP, C-reactive protein; ctrl, control; DAS28, disease activity score in 28 joints; DB, double blind; DMARDs, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; GC, glucocorticoid; HAQ, health assessment questionnaire; MC, multicenter; MTX, methotrexate; OL, open label; OR, odds ratio; pts, patients; PD, power Doppler; RCT, randomized controlled trial; SC, single center; SHS, Sharp-van der Heijde score; SOFI, signals of functional impairment; SSZ, sulfasalazine; VAS, visual analog scale; wks, weeks; yrs, years.