Background In contrast to initiation of biologic therapy, guidelines regarding stopping of this treatment are missing. As a result, the decision of discontinuation is still a challenging aspect in the use of biologic therapy. Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.
Objectives To assess whether joint ultrasonography can predict disease relapse in RA patients in sustained remission, either continuing, tapering or stopping Disease modifying drugs (DMARDs) or biologic therapy in a prospective randomized study.
Methods 157 RA patients in clinical remission, (Disease Activity Score in 28 joints [DAS-28] <2.6 for more than 6-months) receiving treatment with DMARDs and biologic therapy, were randomized into four arms: Arm 1: continue full dose DMARDs and taper biologic therapy by 50% (31 patients); Arm 2: taper both DMARDs and biologic therapy dose by 50% (32 patients); Arm 3: taper DMARDs by 50% and stop biologic therapy (31 patients); Arm 4: stop both DMARDs and biologic therapy (31 patients). Patients' joints were assessed ultrasonographically (Gray scale and Power Doppler) at 40 joints (DAS28 joints + ankles + metatarsophalangeal joints) and were prospectively followed up bi-monthly for 12-months. Control group (32 RA patients) continued their DMARDs and biologic therapy at the same doses. Physicians who evaluated the patients during the study period were blinded to the baseline ultrasound findings. The primary endpoint was sustained remission during 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated.
Results The incidence of relapses was related to study arms: Arm 1: relapse 41.9%, arm 2: 59.3%; arm 3: 67.7%; Arm 4: 77.4%. Kapler-Meier Analysis revealed that time to relapse also varied in the 4 study subgroups: Arm 1: 6.8 ± 2.46; Arm 2: 5.3 ± 2.6; Arm 3: 4.7 ± 2.2; Arm 4: 3.9 ± 2.1 months. Relapse rates were significantly higher in patients whose total ultrasound scores at discontinuation were high than in those whose total ultrasound scores were low (P<0.001 for both total gray-scale and power Doppler scores). Positive and negative predictive values were 84.7% and 71.2% for the total Gray-scale score and 89.8% and 73.5% for the total power Doppler score, respectively. Multivariate logistic regression identified anti-citrullinated protein antibodies (ACPA) positivity (p=0.027) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 1: p 0.004, arm 2: p=0.002; arm 3: p=0.003, arm 4: p=0.001).
Conclusions Less than 40% of the patients remained in remission after tapering or stopping DMARDs and biological therapy. In RA patients in clinical remission, residual synovial inflammation determined by joint ultrasonographic assessment predicted relapse within a short term after discontinuation of the treatment. Relapses occurred mainly in the first 6 months after treatment reduction or stoppage and were associated with the presence of ACPA. This data endorse the establishment of ultrasound-based strategies before optimizing biologic/ DMARs therapy in RA is considered.
Disclosure of Interest None declared