1SUMMARY OF THE MANUFACTURER’S PHARMACOECONOMIC SUBMISSION

The manufacturer submitted a cost-utility analysis that compared ustekinumab with infliximab, adalimumab, vedolizumab, and conventional therapy (including corticosteroids or immunomodulators) for the treatment of moderately to severely active Crohn’s disease (CD). The analysis was conducted from a Canadian public-payer perspective over a 25-year time horizon. Two target populations were included: patients with moderately to severely active CD who had experienced failure with conventional therapy only (FCTO) and patients who had experienced failure with anti-TNF therapy. The analysis also included a mixed population of these, weighted based on the proportion of patient subpopulations in the phase III maintenance trial for ustekinumab, IM-UNITI. The cost-utility analysis evaluated a dosage regimen of every eight weeks and every 12 weeks for ustekinumab, as well as a regimen reflecting the blend of the two doses. The model structure consisted of a decision tree to model the induction-treatment phase and a Markov (cohort) structure to model maintenance treatment for the remainder of the time horizon.

Progression of disease and resulting transition probabilities between health states during the induction phase of treatment were based on a network meta-analysis (NMA) estimating relative treatment effect. For the maintenance phase, another NMA was performed to inform transition probabilities for biologics other than ustekinumab, and the IM-UNITI trial informed the transition probabilities for ustekinumab and conventional therapy. Long-term real-world evidence was used to inform transition probabilities beyond one year. The manufacturer justified the use of such evidence based on the lack of clinical trial data for each biologic treatment beyond approximately one year.

Patients were allocated to one of three outcomes at the end of induction treatment: remission, response, and no-response. The health states in the maintenance-phase Markov model consisted of “response,” “remission,” and “loss of response.” The “loss of response” health state for four model cycles (representing 16 weeks) was classified as a “treatment failure.” Patients experiencing a treatment failure could escalate the dosage as appropriate according to the product’s label, remain in “loss of response” and transition to conventional therapy as appropriate, or undergo surgery. Patients who underwent surgery in the model entered a “post-surgical response” health state. Upon a secondary loss of response after surgery, patients were re-treated with their index biologic and re-entered the model in either the “response” or “loss of response” health state. An optional oral corticosteroid-sparing remission health state was included to reflect the improvement in quality of life and decrease in costs from the subset of patients with a remission who do not require management with oral corticosteroids.¹

Data on health care resource utilization were collected by the manufacturer through a Delphi panel conducted with Canadian clinicians experienced in treating CD. Costs of medications were obtained from the Ontario Ministry of Health and Long-Term Care Exceptional Access Program formulary and from the Ontario Drug Benefit formulary.⁷ Utility values were obtained from a Canadian study by Gregor et al. (1997) for the remission, response, nonresponse, surgery, and post-surgery health states.⁸ Discount rates were applied to both costs and health benefits at a rate of 5%.¹ The manufacturer’s base-case analysis did not include a cost for the intravenous (IV) administration of ustekinumab in the induction phase.