Rheumatoid arthritis (RA) is a chronic inflammatory disease whose natural history leads to articular and extra-articular damage. Both cardiovascular risk and malignancy risk results higher in RA patients, compared to general population. Janus kinase inhibitors (JAKis) are oral targeted synthetic disease modifying antirheumatic drugs (tsDMARDs) that disrupt cytokine cascade and exert anti-inflammatory effects by interfering with signaling through the JAK-STAT intracellular pathways. A recent RCT comparing tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily and anti-TNF in rheumatoid arthritis demonstrated an increased risk of MACE HR 1.33 and cancer HR 1.49 at a follow-up of 4 years. This has led the FDA to class warnings for tofacitinib, baricitinib and upadacitinib. Cumulative RCT data, RCT extension data demonstrated a safety profile for Jak inhibitors. Conflicting data results from real life registries; the different selectivity for JAKs (JAK1, JAK2, JAK3 and Tyk2) probably determines differences in efficacy and safety profiles among the members of this group which should actually be evaluated. In order to better understand the cardiovascular and neoplastic risk linked to these class of drugs, we aim to provide a literature review on existing evidence of the safety of Jak-Inhibitors in rheumatoid arthritis.

Cardiovascular safety, cancer and Jak-inhibitors: Differences to be highlighted / M. Benucci, A. Damiani, M. Infantino, M. Manfredi, B. Lari, V. Grossi, F.L. Gobbi, P. Sarzi-Puttini. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 183:(2022), pp. 106359.1-106359.9. [10.1016/j.phrs.2022.106359]

Cardiovascular safety, cancer and Jak-inhibitors: Differences to be highlighted

P. Sarzi-Puttini
Ultimo
2022

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease whose natural history leads to articular and extra-articular damage. Both cardiovascular risk and malignancy risk results higher in RA patients, compared to general population. Janus kinase inhibitors (JAKis) are oral targeted synthetic disease modifying antirheumatic drugs (tsDMARDs) that disrupt cytokine cascade and exert anti-inflammatory effects by interfering with signaling through the JAK-STAT intracellular pathways. A recent RCT comparing tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily and anti-TNF in rheumatoid arthritis demonstrated an increased risk of MACE HR 1.33 and cancer HR 1.49 at a follow-up of 4 years. This has led the FDA to class warnings for tofacitinib, baricitinib and upadacitinib. Cumulative RCT data, RCT extension data demonstrated a safety profile for Jak inhibitors. Conflicting data results from real life registries; the different selectivity for JAKs (JAK1, JAK2, JAK3 and Tyk2) probably determines differences in efficacy and safety profiles among the members of this group which should actually be evaluated. In order to better understand the cardiovascular and neoplastic risk linked to these class of drugs, we aim to provide a literature review on existing evidence of the safety of Jak-Inhibitors in rheumatoid arthritis.
Baricitinib; Cancer; Cardiovascular events; Filgotinib; Tofacitinib; Upadacitinib
Settore MED/16 - Reumatologia
2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
Cardiovascular safety, cancer and Jak-inhibitors.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 444.79 kB
Formato Adobe PDF
444.79 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1032509
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 14
social impact