PO:08:113 | Shaping rheumatoid arthritis treatment: clinical and demographic drivers of tsDMARDs versus bDMARDs prescription post-EMA pronouncement on JAK inhibitors - insights from the AMBI-RA study

Riccardo Bertola¹, Beatrice Maranini¹, Carlo Garaffoni¹, Maria Pozzuto¹, Anna Laura Riva Cambrino¹, Alessandro Spinelli¹, Letizia Mamprin¹, Federico Agostini¹, Martina Di Nunzio¹, Marcello Govoni¹, Alessandra Bortoluzzi¹, Ettore Silvagni¹ | ¹Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, Italy

Abstract

Background. The AMBI-RA study aimed to assess the influence of clinical and demographic factors on the choice between JAK inhibitors (JAKis), TNF inhibitors (TNFis), and non-TNFi bDMARDs in patients with rheumatoid arthritis (RA), before and after the publication of the EMA safety recommendations on JAKis (January 2023). Six-month outcomes were analyzed to determine whether these recommendations affected the achievement of therapeutic targets.

Materials and Methods. In this single-center, ambidirectional cohort study, clinical, laboratory, and clinimetric data were collected at baseline and after 6 months of follow-up following the initiation of a new therapeutic line with JAK inhibitors (JAKis), TNF inhibitors (TNFis), or non-TNFi bDMARDs in patients with rheumatoid arthritis (RA). Patients were divided into two cohorts: retrospective (pre-EMA) and prospective (post-EMA). The association between clinical and demographic factors and treatment selection was assessed using univariate and multivariate logistic regression analyses. Additionally, we evaluated the relationship between these factors and non-response at 6 months, defined as failure to achieve remission or low disease activity (REM/LDA) according to DAS28-CRP, or early discontinuation of the bDMARD due to lack of efficacy.

Results. A total of 539 treatment courses were analyzed: 300 in the retrospective cohort (pre-EMA: 2019-2022) and 239 in the prospective cohort (post-EMA: 2023-09/2024). Following the EMA safety recommendations, the use of TNFis increased from 32% to 41.4%, while JAKi prescriptions declined from 26% to 16.3%. TNF is also became the most frequently prescribed first-line agents, rising from 51.6% to 74%, whereas JAKis and non-TNFi bDMARDs decreased from 18% to 4.1% and from 30.5% to 21.9%, respectively (Table 1). Except for older age, the EMA-identified risk factors did not significantly influence JAKi prescriptions in the prospective cohort. TNFis were consistently associated with first-line use in both cohorts, while non-TNFi bDMARDs were positively associated with older age and negatively associated with first-line use in the prospective cohort (Tables 2-3). Regarding treatment outcomes at 6 months, remission (REM) rates decreased from 45.1% to 33.1%, low disease activity (LDA) from 58.6% to 49.3%, and non-responder rates increased from 41.8% to 50.6%. Moreover, first-line treatment was the only factor significantly and negatively associated with non-response at 6 months in the retrospective cohort, but not in the prospective one, suggesting a possible loss of the clinical benefit historically linked to first-line therapy (Table 4).

Conclusions. The AMBI-RA study represents the first attempt, through an ambidirectional design, to compare the association between clinical and demographic variables and the prescription of b/tsDMARDs before and after the EMA safety recommendations on JAK inhibitors. The analysis of their impact on the examined cohort suggests a lower effectiveness of first-line treatment strategies, which have shifted predominantly toward TNFis in the post-EMA period. Future multicenter studies are warranted to further explore how regulatory decisions by international agencies may influence therapeutic target achievement in clinical practice.

Keywords

• AIFA and EMA recommendations.
• JAK inhibitors
• Treat-2-target