An official website of the United States government
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Entyvio (Vedolizumab) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Dec.
Vedolizumab (Entyvio) is an integrin receptor antagonist indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to immunomodulators or a tumour necrosis factor (TNF) alpha antagonist; or who have had an inadequate response or intolerance to or have demonstrated dependence on corticosteroids. The manufacturer is requesting reimbursement in line with this indication. Vedolizumab was previously reviewed by CADTH Common Drug Review (CDR) for the treatment of ulcerative colitis.1 The CADTH Canadian Drug Expert Committee recommended that vedolizumab be reimbursed for ulcerative colitis, with the condition of price reduction. The price of vedolizumab for the ulcerative colitis submission is the same as the current price submitted for Crohn’s disease.
Vedolizumab is available in 300 mg/20 mL vials for intravenous infusion at the current market price of $3,290 per vial. The recommended dosing of vedolizumab for Crohn’s disease is 300 mg at 0, 2, and 6 weeks followed by every eight weeks thereafter;2 thus, the cost of approved-dose vedolizumab is $26,320 per patient in the first year and an average of $21,458 per patient in subsequent years.
The manufacturer submitted a cost comparison of vedolizumab to branded infliximab (Remicade) and adalimumab (Humira) in the indicated population. The perspective was that of a public drug payer with a time horizon of two years to incorporate both the induction and maintenance phases of the comparators. The assumption of clinical similarity was based on a manufacturer-funded indirect treatment comparison. Only drug costs were considered, all other health care costs having been assumed to be equal for the different comparators. Costs for infliximab and adalimumab were derived using the Ontario Drug Benefit (ODB) Formulary Exceptional Access Program, while the cost of vedolizumab was derived using the manufacturer’s current market price. Proportions of patients using standard versus escalated doses of infliximab and adalimumab in the base case with the addition of vedolizumab in a sensitivity analysis were derived from the ACCENT I,3,4 CLASSIC II,5 and GEMINI II6,7 trials, respectively.
The manufacturer reported that treatment with approved-dose vedolizumab ($25,571 per patient in year 1 and $21,458 per patient in year 2) would cost $790 and $6,704 less than the dose-weighted cost estimates for adalimumab ($26,361 and $28,162 per patient in years 1 and 2, respectively) and $7,394 and $10,490 less than the dose-weighted cost estimates for branded infliximab ($32,965 and $31,948 per patient in years 1 and 2, respectively) (see Table 4 and Table 5).
No head-to-head trials exist comparing vedolizumab to infliximab or adalimumab for the treatment of patients with Crohn’s disease. The manufacturer submitted indirect treatment comparisons using the Bucher method to compare vedolizumab 300 mg every eight weeks after induction to infliximab 5 mg/kg every eight weeks after induction and to adalimumab 40 mg every two weeks after induction, with placebo as the common comparator in each case. The manufacturer concluded that vedolizumab was noninferior to adalimumab for inducing and maintaining clinical remission (where remission was defined as having a Crohn’s Disease Activity Index [CDAI] ≤ 150), corticosteroid-free clinical remission, and inducing clinical response (reduction in CDAI of ≥ 70) and was noninferior to infliximab for inducing and maintaining clinical remission. However, vedolizumab was not noninferior to adalimumab for maintaining enhanced clinical response (reduction in CDAI ≥ 100) and clinical response and not noninferior to infliximab for inducing and maintaining clinical response. The manufacturer did not pre-specify noninferiority margins nor consider the required statistical power. Additionally, there was substantial heterogeneity in study and patient characteristics in the included studies, particularly regarding the proportion of patients who had previously failed treatment with a TNF alpha inhibitor. Similarly, there was considerable heterogeneity in the included studies of three network meta-analyses identified by CDR reviewers comparing vedolizumab to infliximab and adalimumab, with several outcomes appearing significantly different between comparators. Overall, there is considerable uncertainty associated with the assumption of clinical similarity among treatments (see CDR Clinical Report Appendix 6 and Appendix 7), which could not be examined based on the cost comparison submitted.
Inflectra, a subsequent entry biologic (SEB) infliximab, is substantially less expensive than branded infliximab. SEB infliximab recently received a Notice of Compliance from Health Canada for the treatment of adult patients with Crohn’s disease similar to that of branded infliximab.8,9 Should public drug plans reimburse SEB infliximab, it would be considerably less expensive than vedolizumab under all reasonable dose-escalation assumptions. SEB infliximab was included in CDR reanalyses.
There is variability in the relative cost of vedolizumab based on the range of doses that may be used for each comparator. The manufacturer estimated the proportion of patients using each treatment who would escalate to higher-dose regimens based on data from the ACCENT I (infliximab),3,4 CLASSIC II (adalimumab),5 and GEMINI II (vedolizumab; applied for the sensitivity analysis only — it was assumed that no patient experienced dose escalation in the manufacturer base case for vedolizumab as opposed to comparators)6,7 trials. These data are not, however, comparable, due to differences in patient characteristics, escalation criteria, study design, and level of reporting detail between trials. As applied to the manufacturer base case, CDR considered it was inappropriate to assume that the absence of recommended escalation for vedolizumab implies it is equally effective to proportionally weighted average doses combining patients using both standard and escalated doses of either infliximab or adalimumab. The manufacturer’s submitted indirect treatment comparison justifying the use of a cost comparison was conducted using standard-dose trial data for each comparator (see CDR Clinical Report, Appendix 6).
In a sensitivity analysis, the manufacturer assumed that 47.2% of vedolizumab patients received a single additional dose at week 10 before returning to dosing every eight weeks. This is not aligned with the GEMINI II trial, which reported that 47.2% of patients had not responded at week 6 to vedolizumab induction and were provided vedolizumab every four weeks thereafter.6,7
The administration costs of biologic products for the treatment of Crohn’s disease in Canada are currently borne by the manufacturer. Should this change in future, subcutaneous injections as well as less frequent infusion schedules, faster infusing times, or both may become relatively more attractive from a cost perspective.
CDR’s clinical expert considered it highly likely that patients using vedolizumab who experienced a secondary loss of response (i.e., initially responded but then worsened) would be escalated to higher doses of vedolizumab as is current clinical practice with adalimumab and infliximab. A maintenance dose of 300 mg vedolizumab every four weeks was included in the GEMINI II trial,6,7 although doses higher than the approved 300 mg every eight weeks were not included in the product monograph.2
In CDR’s reanalysis, at the submitted price of $3,290 per 300 mg vial, and at the approved dose of vedolizumab and standard doses of the comparators, the cost of branded infliximab ($31,602 per patient) is $5,282 (20%) more than the cost of vedolizumab ($26,320 per patient); adalimumab ($22,211 per patient) is $4,109 (16%) less than vedolizumab; and SEB infliximab ($16,800 per patient) is $9,520 (36%) less than vedolizumab when comparator drug costs are based on the ODB Formulary Exceptional Access Program list prices. In subsequent years, the cost of branded infliximab ($25,765 per patient) is $4,306 (20%) more than the cost of vedolizumab ($21,458 per patient); adalimumab ($19,315 per patient) is $2,143 (10%) less than vedolizumab; and SEB infliximab ($13,697 per patient) is $7,762 (36%) less than vedolizumab. There is, however, considerable uncertainty in the clinical similarity between vedolizumab and infliximab or adalimumab for this patient population.
Clinical experts have deemed the comparator treatments presented in Table 1 to be appropriate. Comparators may be recommended (appropriate) practice versus actual practice. Comparators are not restricted to drugs, but may be devices or procedures. Costs are from the ODB Formulary Exceptional Access Program (July 2016), unless otherwise specified. Existing Product Listing Agreements are not reflected in the table and as such may not represent the actual costs to public drug plans.
Cost Comparison Table of Biologics for the Treatment of Crohn’s Disease.
Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/
Your browsing activity is empty.
Activity recording is turned off.
See more...
