It looks like you are using an older version of Internet Explorer which is not supported. We advise that you update your browser to the latest version of Microsoft Edge, or consider using other browsers such as Chrome, Firefox or Safari.

Home > Mechanism of Action

The JAK/STAT pathway plays a critical role in GvHD pathophysiology1

The JAK/STAT signalling pathway contributes to the immune response which causes GvHD.1

JAK1/JAK2 signalling in GvHD pathogenesis

JAK1/JAK2 signalling is critical to the activation of neutrophils, which are involved in the pathogenesis of acute GvHD.2

Neutrophil activation in GvHD pathogenesis

JAK/STAT signalling plays an important role in immune cell activation and tissue inflammation affecting T-cell activation and survival, which is implicated in the development of GvHD.3

Until now, there have been no approved therapies that inhibit JAK signalling in GvHD1,4,5

JAKAVI has a unique mechanism of action in GvHD

JAKAVI inhibits JAK1 and JAK2 signalling in GvHD.1

JAK1/JAK2 inhibition with JAKAVI

JAKAVI inhibits JAK1 and JAK2 signalling in GvHD, suppressing cytokine production and T-cell expansion and promoting regulatory T-cell development to suppress donor T-cell proliferation.6

JAKAVI inhibits JAK1 and JAK2 signalling in GvHD without negatively affecting graft-vs-leukemia activity7

References
  1. JAKAVI® (ruxolitinib) tablets: EU Summary of Product Characteristics. Novartis; January 2022.
  2. Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host-disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062-2068.
  3. Spoerl S, Mathew NR, Bscheider M, et al. Activity of therapeutic JAK ½ blockade in graft-versus-host-disease. Blood. 2014;123(24):3832-3842.
  4. Zeiser R, von Bubnoff N, Butler J, et al; REACH2 Trial Group. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810.
  5. Zeiser R, Polverelli N, Ram R, et al; REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238.
  6. Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbar B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GvHD: an introduction to the REACH trials. Immunotherapy. 2018;10(5):391-402.
  7. Choi J, Cooper ML, Alahmari B, et al. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLoS One. 2014;9(10):e109799.