AB0562 THE EFFECTS OF TOFACITINIB IN SIMULTANEOUSLY IMPROVING GLYCAEMIC PARAMETERS AND INFLAMMATORY MARKERS IN RHEUMATOID ARTHRITIS PATIENTS WITH COMORBID TYPE 2 DIABETES. A PROOF-OF-CONCEPT, OPEN, PROSPECTIVE, CLINICAL STUDY (2024)

Abstract

Background: A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance, and type 2 diabetes (T2D) [1]. The β-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent by JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation [2]. Considering that JAK inhibitors (JAKis) are successfully used in RA, it could be theoretically hypothesized that these drugs could bidirectionally improve inflammatory signs and associated glucose abnormalities in patients with T2D. In fact, according to previous findings [3-5], the administration of some RA-specific therapies could target the mechanisms of the concomitant cardiometabolic comorbidity providing a study model to be applied in this context.

Objectives: On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D in a proof-of-concept, open, prospective, clinical study.

Methods: The primary endpoint was the change in homeostatic model assessment 2 of insulin resistance (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib [6]. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters.

Conclusion: The administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a “bidirectional” benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.

Acknowledgements: NIL.

Disclosure of Interests: Piero Ruscitti Pfizer, Claudia Di Muzio: None declared, Ilenia Di Cola: None declared, Azadeh Shariat Panahi: None declared, Federica Sensini: None declared, Francesco Ursini: None declared, Annamaria Iagnocco: None declared, Roberto Giacomelli: None declared, Paola Cipriani: None declared.