TA880 · STA
Recommended in routine commissioning for treating severe asthma in people 12 years and over, when treatment with high-dose inhaled corticosteroids plus another maintenance treatment has not worked well enough. Only if: people have had 3 or more exacerbations in the previous year or are having maintenance oral corticosteroids, and the company provides tezepelumab according to the commercial arrangement.
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| standard care (high-dose inhaled corticosteroids plus another maintenance treatment) | standard of care | Yes | — |
| standard care plus add-on biological treatments | active drug | Yes | — |
| placebo | placebo | — | — |
| omalizumab | active drug | Yes | — |
| reslizumab | active drug | Yes | — |
| benralizumab | active drug | Yes | — |
| mepolizumab | active drug | Yes | — |
| dupilumab | active drug | Yes | — |
| standard care alone | standard of care | Yes | — |
| standard care | standard of care | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| PATHWAY | RCT | Phase 3 | Yes |
| NAVIGATOR | RCT | Phase 3 | Yes |
| SOURCE | RCT | Phase 3 | Yes |
Economic model
Methodological decisions (16)
Selection of appropriate comparators for tezepelumab. Committee agreed that standard care (high-dose inhaled corticosteroids plus another maintenance treatment) with or without add-on biological treatments are relevant comparators.
Committee: Standard care with or without add-on biological treatments
ICER impact: negligible
Company used network meta-analysis (NMA) to compare tezepelumab with biological treatments. NMAs had considerable uncertainty due to unresolvable limitations in evidence and mismatch between trial biomarkers and NICE-recommended treatment biomarkers.
Company: NMAs provided robust comparisons; company updated NMA inputs to address concerns and provided scenarios based on simulated treatment comparison and published NMAs
ERG: Original and updated NMAs both had considerable uncertainty; biomarker evidence in trials did not all match biomarkers used for NICE-recommended treatments
Committee: Tezepelumab is likely to have similar clinical effectiveness compared with existing biological treatments, but this was highly uncertain
ICER impact: uncertain_direction
Subgroup selection for NMA comparisons: baseline blood eosinophil count thresholds
Company: Used subgroup with baseline blood eosinophil count at least 300 cells per microlitre for reslizumab, mepolizumab, benralizumab
ERG: Preferred subgroup with baseline blood eosinophil count at least 150 cells per microlitre for dupilumab comparison
Committee: Company's updated NMA using ≥300 cells/µL for reslizumab/mepolizumab/benralizumab; EAG's preferred ≥150 cells/µL for dupilumab
ICER impact: uncertain_direction
Company used 5-state Markov model with health states: controlled asthma, uncontrolled asthma, uncontrolled asthma with exacerbation, controlled asthma with exacerbation, and dead
Company: 5-state model is appropriate
ERG: Model structure appropriate but uncertain about approach of modelling exacerbations as controlled and uncontrolled
Committee: Model structure is appropriate for decision making
ICER impact: negligible
Company's approach of modelling asthma exacerbations in controlled and uncontrolled states; model prohibited transitions from controlled asthma to uncontrolled asthma with exacerbation and from uncontrolled asthma to controlled asthma with exacerbation
Company: Approach is appropriate; distinguishing between exacerbations in previously controlled asthma from asthma not previously controlled captures differences in health-related quality of life, costs and mortality
ERG: Considered it inappropriate; transition probabilities from exacerbation health states to controlled asthma state may have been overestimated; clinical opinion suggested people can have exacerbations in any health state with different risk depending on starting health state
Committee: Company's approach is acceptable for decision making
ICER impact: increases
Asthma-related mortality estimates in model; company originally assumed deaths from asthma could only occur through exacerbations; company later provided UK-based real-world study from CPRD
Company: Original asthma-related mortality estimates were appropriate; later provided CPRD analysis showing all-cause mortality for people with severe asthma was substantially higher than predicted
ERG: Originally considered company's probabilities overestimated asthma-related mortality for people younger than 75 years; re-estimated based on 2020 ONS mortality data; later acknowledged CPRD analysis was well done and reduced uncertainty but had limitations in applicability
Committee: Company's original base-case asthma-related mortality estimates were more appropriate but CPRD analysis was informative for non-biological eligible group; will consider cost-effectiveness scenarios using both estimates
ICER impact: increases
Asthma-related mortality estimates for people younger than 75 years
Company: Deaths from asthma only through exacerbations; original base-case estimates
ERG: EAG re-estimated using 2020 Office of National Statistics mortality data, resulting in lower probability (0.001 per 4-weekly cycle)
Committee: Company's original base-case asthma-related mortality estimates more appropriate, but CPRD analysis informative for non-biological eligible group; consider both scenarios
ICER impact: decreases
Application of real-world CPRD mortality data across all subgroups vs only non-biological eligible subgroup
Company: Applied CPRD-based all-cause mortality results across all subgroups
ERG: Should apply overall population estimates across all subgroups or estimate and apply mortality rates by subgroup individually; multiplier used was uncertain due to limited sample size; calibrating exacerbation-related mortality to all-cause mortality may have overestimated
Committee: Will consider cost-effectiveness scenarios using both original base-case asthma-related mortality estimates and CPRD data (only in non-biological eligible subgroup)
ICER impact: decreases
Definition of clinical response to tezepelumab for ongoing treatment continuation. Company initially proposed any reduction in exacerbations or oral corticosteroids dose. EAG considered this inappropriate and proposed 20-50% reduction. Committee and stakeholders (supported by clinical opinion from severe asthma specialists) agreed on updated definition: 50% reduction in exacerbations for people not on maintenance oral corticosteroids; 50% reduction in oral corticosteroid dose for those on maintenance therapy.
Company: Any reduction in exacerbations or oral corticosteroids dose constitutes treatment response
ERG: 20-50% reduction in exacerbations is appropriate treatment response
Committee: 50% reduction in exacerbations (for people not on oral corticosteroids) or 50% reduction in oral corticosteroid dose (for those on maintenance therapy)
ICER impact: uncertain_direction
ACQ-6 cut-off score to define asthma control status in model
Company: Using ACQ-6 cut-off score of 1.5 to define asthma control (controlled <1.5, uncontrolled >1.5); company considered using partially controlled asthma as third health state but did not implement due to multiple subgroups being considered
ERG: Preferred using cut-off of 1 based on Juniper et al. (2006) study suggesting crossover point close to ACQ-6 score of 1; considered cut-off of 1.5 would misclassify some asthma and overestimate treatment effectiveness
Committee: Using ACQ-6 score of 1.5 as cut-off is appropriate; clinical expert agreed with company's approach
ICER impact: negligible
Definition of responder to treatment (only those who respond continue in model)
Company: Company proposed responder definition
Committee: Company's updated treatment response definition acceptable
ICER impact: not specified
Whether trial populations (PATHWAY, NAVIGATOR, SOURCE) are representative of NHS patients with severe asthma. Clinical experts and EAG noted well-balanced baseline characteristics and considered populations reflective of NHS severe asthma patients.
Committee: Trial populations are generally representative of NHS patients
ICER impact: negligible
Company included one-off stopping at 52 weeks in model; after 52 weeks, different transition probabilities applied for people whose asthma was considered to have responded
Company: Approach reflects stopping rules in previous NICE technology appraisals for other add-on biological treatments; appropriate to have different transition probabilities for responders after 52 weeks
ERG: Overestimated treatment effect because stopping had been accounted for; set transition probabilities before and after 52 weeks to be equal as conservative approach due to lack of data
Committee: Company's approach is acceptable
ICER impact: increases
Duration and magnitude of exacerbation reduction/maintenance oral corticosteroid dose reduction
Company: Not explicitly stated
Committee: 50% reduction in exacerbations for those without maintenance oral corticosteroids; 50% reduction in oral corticosteroid dose for those on maintenance
ICER impact: not specified
Additional utility increment for people receiving biological treatments beyond health state utilities
Company: Applied utility gain not associated with health state; based on EQ-5D-5L regression analysis from tezepelumab trials; aligned with benralizumab and omalizumab precedent
ERG: Effectiveness should be reflected in modelled health states; adding additional utility increment with borderline statistical significance inappropriate; in benralizumab/omalizumab precedent, biological treatment utilities were attached to health states
Committee: Company's updated approach appropriate after removing non-significant biological-specific utility gain
ICER impact: decreases
Company assumed utility increment for people who had a biological treatment, not associated with any health state in model
Company: Utility increment applied because benefits of treatment were not captured by model health states
ERG: Not explicitly stated in chunk
Committee: Committee questioned face validity; company explained approach
ICER impact: increases
Evidence gaps
Commercial arrangement
Special considerations
Cross-references