Intensive therapy alleviates subclinical synovitis on ultrasound and disease activity and reduces flare in rheumatoid arthritis patients who have achieved clinical target – a randomized controlled trial

Abstract

ObjectiveWhether intensive therapy can alleviate subclinical synovitis and reduce flare in rheumatoid arthritis (RA) patients in clinical remission remains unclear. We designed a 1-year open-labelled, randomized controlled clinical trial to elucidate this question. MethodsRA patients in clinical remission/low disease activity (defined by DAS28-CRP≤ 3.2), however with subclinical synovitis on ultrasound [power Doppler (PD)≥1 and/or gray scale (GS)≥2] were randomized to receive maintenance or intensive treatment at a ratio of 1:1. The primary outcome was the rate of RA relapse (defined by DAS28-CRP>3.2 and an increase≥0.6). The secondary outcomes were changes of PD and GS scores, and clinical disease activity at each visit from baseline. Results108 patients with 54 in each group were enrolled. During 1-year follow-up, the relapse rate was significantly higher in maintenance group than in intensive group, regardless of all enrolled patients or those in remission [24.1% (13/54) vs. 9.1% (5/54), p=0.039; 26.2% (11/42) vs. 5.3% (2/38), p=0.026, respectively]. Although GS and PD scores were decreased at 12 months in both groups, the decline was more remarkable in intensive group than in maintenance group. The improvement of clinical disease activity score was only observed in intensive group, not maintenance group. Adverse events were comparable between two groups. Abnormal liver function tests were observed in 24 (22%) patients with 16 from intensive group. ConclusionIntensive therapy can alleviate subclinical synovitis on ultrasound and clinical disease activity, and prevent relapse in RA patients who have achieved clinical remission or low disease activity, with comparable safety profiles to maintenance therapy. Registration numberChiCTR2000029279