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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

  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.