The Pharmaceutical Benefits Scheme (PBS) listing for ruxolitinib has been expanded. The listing now includes acute or chronic graft-versus-host disease (GvHD) in patients with an inadequate response to corticosteroids.
Ruxolitinib is an inhibitor of the Janus Associated Kinases (JAKs), JAK1 and JAK2. Inhibition of these enzymes disrupts cytokine and growth factor signalling pathways involved in the pathogenesis of GvHD. The REACH 2 and REACH 3 studies investigated the safety and efficacy of ruxolitinib compared to control (investigator’s choice of commonly used therapies) in glucocorticoid-refractory GvHD.
The REACH 2 trial was undertaken in patients with acute GvHD. At day 28, the overall response was 62% in the ruxolitinib group compared to 39% in the control group. The REACH 3 trial was conducted in patients with chronic GvHD. At week 24, the overall response was 49.7% in the ruxolitinib group and 25.6% in the control group.
Ruxolitinib is an oral medication with a usual starting dose of 10mg twice daily in chronic GvHD and 5-10mg twice daily in acute GvHD. The dose may require adjustment according to patient response and toxicity or due to interacting drugs. Ruxolitinib is metabolised by CYP3A4 and CYP2C9; the manufacturer recommends halving the dose when administered with dual moderate inhibitors of these enzymes, such as fluconazole ≤ 200mg daily (higher doses of fluconazole should be avoided).
References:
- Jakavi® (Ruxolitinib) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals. Approved October 2022.
- Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021; 385(3): 228-38.
- Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020; 382(19): 1800-10.
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