A Multi-State Model to Assess the Impact of Ruxolitinib in Extending Failure Free Survival and Life Expectancy in Patients With Steroid-Refractory Acute Graft vs Host Disease

Speaker(s)

Zebrowska K1, Bao X2, Moawad M2, Woodcock F2, Prieto N3, Rafia R4, Bennett N1, Jameson K1
1Novartis Pharmaceuticals UK Limited, London, London, UK, 2Source Health Economics, London, LON, UK, 3Novartis de Colombia S.A., Bogota, Bogota, Colombia, 4Novartis Pharmaceuticals UK Limited, London, UK

OBJECTIVES: Acute graft vs host disease (aGvHD) is a serious immune reaction occurring in patients who receive allogeneic stem cell transplant (alloSCT), characterised by systemic inflammation and ultimately, tissue destruction affecting multiple organs. AGvHD is a significant cause of early mortality, especially amongst steroid refractory (SR) patients, with reported mortality rates of 90% at 4 years. The Phase 3 REACH2 trial demonstrated the efficacy of ruxolitinib compared to best available therapy (BAT) for SR aGvHD, with statistically significant improvements in overall response rate and failure-free survival (FFS). This analysis estimates extensions of FFS and life expectancy for patients treated with ruxolitinib.

METHODS: A multi-state model was developed, with health states defined using the components of FFS: failure-free, new systemic treatment, relapse of underlying disease, and death. AGvHD patients are also at risk of developing chronic GvHD (cGvHD). Any change in mortality in the acute phase could impact the proportion of patients that develop cGvHD, therefore cGvHD was included in the model. Transition probabilities to inform movement between the aGvHD states and developing cGvHD were derived from REACH2. Transition probabilities for cGvHD were derived from the BAT arm of REACH3, a phase 3 trial investigating the efficacy of ruxolitinib vs BAT for SR-cGvHD.

RESULTS: SR-aGvHD patients treated with ruxolitinib gained an average of 0.58 additional years of FFS and 1.23 additional life-years (LYs) compared with BAT. The model predicts that patients in the ruxolitinib arm were also more likely to develop cGvHD (49% vs 36%) as they were less likely to experience another competing event, and 0.75 of the additional LYs were gained in cGvHD states.

CONCLUSIONS: SR-aGvHD is a severe disease with poor life expectancy. The model predicts that patients treated with ruxolitinib experience an increase in their FFS and gain additional LYs, showing ruxolitinib addresses an important unmet need.

Code

EE604

Topic

Economic Evaluation

Topic Subcategory

Cost-comparison, Effectiveness, Utility, Benefit Analysis

Disease

Oncology, Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)