Study shows 'bidirectional' benefit of tofacitinib in rheumatoid arthritis patients with comorbid type 2 diabetes: Study

Previous studies have shown a connection between rheumatoid arthritis, insulin resistance, and type 2 diabetes. The β-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression of pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. Tofacitinib is a potent and selective JAK inhibitor. 

Against the above background, Piero Ruscitti, University of L’Aquila, Delta 6 Building, L’Aquila, Italy, and colleagues aimed to evaluate if tofacitinib administration could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D.

The study's primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) following 6 months of tofacitinib treatment in RA patients with type 2 diabetes. The proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib, included consecutive RA patients with T2D diagnosis. Additional endpoints regarding RA disease activity and metabolic parameters were also assessed.

Forty consecutive rheumatoid arthritis patients with type 2 diabetes were included (female sex 68.9%, the mean age of 63.4 ± 9.9 years).

The study led to the following findings:

· During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib.

· Tofacitinib demonstrated a significant effect on the overall reduction of HOMA2-IR (β = − 1.1). Also, HOMA2-β enhanced in these patients highlighting an improvement of insulin sensitivity.

· Although there is a need for longer follow-up, a trend in glycated haemoglobin reduction was also recorded.

· The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response.

· No major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and thromboembolic and/or cardiovascular events were recorded.

"Tofacitinib administration in rheumatoid arthritis with type 2 diabetes led to a simultaneous improvement of inflammatory disease activity and insulin resistance, leading to a “bidirectional” benefit in these patients with concomitant rheumatic and metabolic diseases," the researchers wrote.

"Further powered and specifically designed studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D," they concluded.

Reference:

Di Muzio, C., Di Cola, I., Shariat Panahi, A. et al. The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study. Arthritis Res Ther 26, 14 (2024). https://doi.org/10.1186/s13075-023-03249-7