Background/Purpose: 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. 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 6 months of therapy (crude difference of 0.93 of glycated haemoglobin, HbA1c% between groups). Concerning RA, a progressive reduction of disease activity was observed in both groups. 

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, including the rate of reduction and discontinuation of both antidiabetic drugs and glucocorticoids (GCs).

Methods: In this study, participants with RA and T2D, 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.

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 with active disease (DAS28: 5.54 ± 1.03; C-reactive protein 11.84 ±9.67 mg/L) 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 participants, with a percentage of participants 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 GCs therapy. Analysing the safety profile, as observed in first 6 months of the study, only minor side effects were recorded during the whole follow-up with no difference between groups, except for self-limited urticarial lesions at the injection site which were more frequently in anakinra-treated participants.

Conclusion: Data deriving from the long-term extension of participants with RA and T2D, enrolled in the TRACK study, showed that the benefits of IL-1 inhibition on metabolic and inflammatory parameters lasted longer than the first 6 months of follow-up. Thus, the presence of T2D could identify a subset of RA patients likely benefitting of IL-1 inhibition. Finally, the achievement of optimal therapeutic targets for both RA and T2D might significantly improve the cardiovascular burden of these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reaching-remission-by-il-1-inhibition-in-rheumatoid-arthritis-patients-with-type-2-diabetes-improves-the-glucose-homeostasis-long-term-findings-from-track-study-a-multicentre-open-label-randomised/