THU0148 EFFICACY OF IL-1 INHIBITION ON RHEUMATOID ARTHRITIS AND TYPE 2 DIABETES, LONG-TERM FINDINGS FROM TRACK STUDY, A MULTICENTRE, OPEN-LABEL, RANDOMISED CONTROLLED TRIAL

Abstract

Background: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets by using biologic DMARDs designed for rheumatoid arthritis (RA), and IL-1 would be a common pathogenic mediator, suggesting a possible common therapeutic target [1]. In TRACK study, a multicentre open-label, randomised controlled trial, anakinra, a human interleukin-1-receptor antagonist, showed to induce a significant improvement of metabolic alteration whereas TNFi did not show any significant improvement on that, after both 3 months and 6 months of therapy (crude difference of 0.93 of glycated haemoglobin, HbA1c% between groups) [2]. Concerning RA, a progressive reduction of disease activity was observed in both groups [2]. Objectives: Since TRACK study has been prematurely stopped for “early benefit” after 6 months of follow-up, in this work, we aimed at investigating how long lasted the improvement of HbA1c% and of RA disease activity, considering the original scheduled 24 months follow-up. We also assessed the rate of antidiabetic and anti-rheumatic therapies reduction and stoppage. Methods: This study was designed as a multicentre, open-label, randomised controlled trial, enrolled participants, with RA and T2D, in 12 Italian Rheumatologic Units, between 2013 to 2016. Participants were randomised to anakinra or to a TNFi and the primary endpoint was the change in HbA1c% (EudraCT: 2012-005370-62; ClinicalTrial.gov: NCT02236481). In this further evaluation, we assessed how long lasted the improvement of HbA1c% and of RA disease activity, considering the original scheduled 24 months follow-up, and the rate of antidiabetic and anti-rheumatic drugs, mainly focusing on steroids, reduction and stoppage. Results: In TRACK study, 39 participants with RA and T2D (age 62.72 ± 9.97, 74.4% female gender) were randomised to anakinra or to TNFi; the majority of participants had seropositive RA disease (rheumatoid factor and/or ACPA 70.2%) with active disease (DAS28: 5.54 ± 1.03; C-reactive protein 11.84 ±9.67 mg/L, respectively) and all participants had T2D (HbA1c%: 7.77 ±0.70, fasting plasma glucose: 139.13 ±42.17 mg). Considering the last available observation, a maintenance of reduced levels of HbA1c% was observed in anakinra-treated participants (Baseline: 7.73% ±0.67; 6 months: 6.70% ±0.67; last follow-up: 6.60% ±0.52). Paralleling with HbA1c%, a significant reduction of dosages of antidiabetic therapies was observed in anakinra-treated patients, with a percentage of patients who discontinued any anti-diabetic therapy. Conversely, an intensification of antidiabetic therapies was reported in TNFi-treated participants. Concerning RA, the clinical response was maintained during the whole follow-up, although a larger percentage of anakinra-treated participants discontinued the concomitant steroids therapy. Conclusion: In this study, we observed the benefit of IL-1 inhibition in patients with RA and T2D, reaching the therapeutic targets of both diseases, which lasted longer than first 6 months of follow-up. Although the limitations due to open-label design and the necessity of further confirmatory studies, our results could suggest the concept that IL-1 inhibition may be considered a targeted therapeutic strategy for RA and T2D.