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(1): 14, 2024 01 04.
Article
em En
| MEDLINE
| ID: mdl-38178250
ABSTRACT
BACKGROUND:
A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The ß-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 on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. 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.METHODS:
The primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (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. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters.RESULTS:
Forty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (ß = - 1.1, p = 0.019, 95%CI - 1.5 to - 0.76). Also, HOMA2-ß enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, 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. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Antirreumáticos
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Diabetes Mellitus Tipo 2
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article