Clinical and Ultrasonographic Remission in Bio-naïve and Bio-failure Patients with Rheumatoid Arthritis at 24 Weeks of Upadacitinib Treatment: The UPARAREMUS Real-Life Study

Abstract

Introduction: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study.

Methods: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints.

Results: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve.

Conclusions: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Keywords: Clinical remission; JAK inhibitors; Ultrasonographic remission; Upadacitinib.

Fig. 1

a Percentage of patients reaching clinical and clinical plus US  remission at 12 (T1) and 24 weeks (T2). b Proportion of patients with US remission among total patients in clinical remission at T1 and T2

Fig. 2

a Disease activity form baseline to T1 and T2; b remission rates with different indices at T1 and T2. CDAI clinical disease activity index, DAS 28 Disease Activity Score on 28 joints, SDAI simplified disease activity index, T1 12-week follow-up, T2 24-week follow-up

Fig. 3

Representatives examples of PD synovitis at T0 and T1 in two patients. a T0 severe synovitis of the second metacarpophalangeal (MCP) joint of right hand, PD grade 2. b T0 severe synovitis of the left radiocarpal joint, PD grade 3. c T1 moderate synovitis of the second MCP joint of right hand, PD negative. d T1 mild synovitis of the left radiocarpal joint, PD negative. PD power Doppler, T1 12-week follow-up, T2 24-week follow-up