title: Ruxolitinib for the treatment of myelofibrosis: a NICE single technology appraisal.
abstract: The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ruxolitinib (Novartis) to submit clinical and cost-effectiveness evidence for ruxolitinib within its licensed indication (the treatment of disease-related splenomegaly or symptoms in adult patients with myelofibrosis), according to the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA289 issued in June 2013. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The main clinical effectiveness data were derived from two phase III, multicentre, randomised controlled trials (RCTs): Controlled myelofibrosis study with oral JAK inhibitor treatment (COMFORT)-II compared ruxolitinib with best available therapy (BAT), and COMFORT-I compared ruxolitinib with placebo. These RCTs demonstrated that ruxolitinib confers significant benefits in terms of spleen size reduction and improvement in symptom burden. In the COMFORT-II trial, a reduction in spleen volume of ≥35 % was achieved in 28 % of ruxolitinib-treated patients compared with 0 % of patients in the BAT group (p < 0.001) at 48 weeks, and there was a mean change in spleen volume of -30.1 versus +7.3 % (p < 0.001). Ruxolitinib also provided significant improvements in myelofibrosis-associated symptoms and health-related quality-of-life compared with BAT and placebo. The ERG concluded that ruxolitinib appears to reduce splenomegaly and its associated symptoms, but that there was considerable uncertainty surrounding the manufacturer's cost-effectiveness estimates due to limitations in the manufacturer's model. The manufacturer's model did not allow for disease progression, did not accurately capture symptomatic relief, had several implausible or unjustified assumptions, and there were several parameter choices that the ERG found sub-optimal. ERG sensitivity analyses found that nearly all plausible adjustments to the model reduced the cost effectiveness of ruxolitinib. It is very likely that the base-case incremental cost-effectiveness ratio of £73,980/quality-adjusted life-year presented by the manufacturer represents a best-case scenario. The NICE Appraisal Committee concluded that ruxolitinib was clinically effective, but could not be considered a cost effective use of National Health Service (NHS) resources for treating disease-related splenomegaly or symptoms in adults with myelofibrosis. Ruxolitinib is not recommended for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia vera myelofibrosis and post-essential thrombocythaemia myelofibrosis in NICE TA289.
authors.affiliation: Centre for Reviews and Dissemination (CRD), University of York, York YO10 5DD, UK, ros.wade@york.ac.uk.
authors.forename: Ros
authors.initials: R
authors.lastname: Wade
authors.forename: Micah
authors.initials: M
authors.lastname: Rose
authors.forename: Aileen Rae
authors.initials: AR
authors.lastname: Neilson
authors.forename: Lisa
authors.initials: L
authors.lastname: Stirk
authors.forename: Rocio
authors.initials: R
authors.lastname: Rodriguez-Lopez
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.forename: Dawn
authors.initials: D
authors.lastname: Craig
authors.forename: Nerys
authors.initials: N
authors.lastname: Woolacott
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D011720:Pyrazoles / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D013163:Splenomegaly / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases