Table S1 Key model assumptions Assumption Justification Transitions between health states Constant exacerbation through time and treatment duration. Exacerbations classified into clinically significant and clinically significant severe. The available data consisted of the number of exacerbations and number of patients per treatment group over the follow-up of the RCTs. The classification of exacerbations corresponded to the severe trial
classification used in the RCTs. mortality Patients in the day-to-day state are at increased risk of death. The literature on asthma supports that patients with persistent allergic asthma are at increased risk of death than the general population. Cycle length First cycle is 16 weeks; The length of the first cycle
Omalizumab revert to standard therapy. Omalizumab are assumed to remain responders for the duration of treatment. standard therapy. Responders are assumed to remain on omalizumab based on clinical advice that patients are mostly adherent to this treatment. Adverse effects from omalizumab Not considered. Adverse effects from omalizumab are mostly
mild. Serious adverse effects are rare. Long-term effects of OCS Incorporated in scenario analysis for maintenance OCS subgroup. Infrequent OCS bursts due to clinically significant exacerbations do not increase the risk of OCS-related adverse effects and have Maintenance use of OCS is associated with adverse effects (ref). No information was found on the additional risk of infrequent short term courses of OCS or on the additional risk following
omalizumab treatment is discontinued. Patients who do not receive omalizumab receive maintenance OCS for the remainder of their life. Treatment duration and time horizon Lifetime horizon. Treatment duration was assumed to be 10 years. Treatment duration was based on the previous analyses of omalizumab effectiveness
and clinical advice. Treatment effect The results of INNOVATE and IA-05 EUP are generalisable to the UK NHS. Omalizumab reduces exacerbation as reported in INNOVATE for adults and adolescents and IA-05 EUP in children. No RCTs conducted solely in the UK NHS were identified. Patients on omalizumab The RCTs evaluating trial
quality of life experience higher HRQoL in day-to-day symptoms than patients on standard care only. Exacerbations are associated with HRQoL, independent of treatment. omalizumab in the UK/EU licensed population collected data on the improvement in HRQoL conferred by omalizumab that is used in the analysis. Resource use and costs Costs of omalizumab estimated using the dose distribution observed in Resource use associated with the administration and monitoring
INNOVATE and IA-05. Initiation of omalizumab requires one initiation appointment with respiratory consultant. Administration by specialist asthma nurse assumed to take 10 minutes. Monitoring by specialist asthma nurse assumed to of omalizumab was on previous assessments and clinical advice. effectiveness
Table S2 Model inputs for hospitalisation subgroup Adults and adolescents (patients ≥ 12 years) Children (patients 6-11 Variables Value (95% confidence interval) Source Value Source Baseline annual rate of exacerbations CSNS exacerbations 0.8706 (0.6308 to 1.2016) INNOVATE Hospitalisation () 2.1429 (3.5545 to 1.2918) IA-05 EUP hospitalisation () CSS exacerbations 1.2235 (0.9323 to 1.6057) INNOVATE hospitalisation () 1.2857 (0.6690 to 2.4711) IA-05 EUP hospitalisation () Treatment Proportion of responders 56.63% (45.96% to 67.29%) INNOVATE hospitalisation () 54.05% (38.00% to 70.11%) IA-05 EUP hospitalisation () Risk ratio for CSNS exacerbations (responders) 0.5902 (0.3137 to 1.1103) INNOVATE hospitalisation () 0.2593 (0.1006 to 0.6682) IA-05 EUP hospitalisation () Risk ratio for CSS exacerbations (responders) 0.2907 (0.1433 to 0.5900) INNOVATE hospitalisation () 0.1440 (0.0311 to 0.6666) IA-05 EUP hospitalisation () Mortality All-cause mortality UK life-tables adjusted for asthma-related deaths. ONS (); deterministic UK life-tables adjusted for deaths. ONS (); deterministic
Asthma-related deaths Asthma-related mortality rate = 0.4 per 100 De Vries et al (2010) () Asthma-related mortality rate = 0.4 per 100 person-years De Vries et al (2010) () HRQoL Omalizumab effect on HRQoL HRQoL difference observed in the 0.761 (omalizumab) versus 0.631 (standard care) hospitalisation () No HRQoL difference between treatments up to age 12. From age 12, HRQoL difference as adults and adolescents. EXALT hospitalisation () loss due to exacerbations CSNS = -0.10 CSS = -0.20 Lloyd et al (2007) () CSNS = -0.10 CSS = -0.20 Lloyd et al (2007) () Duration of exacerbation 4 weeks Lloyd et al (2007) () 4 weeks Lloyd et al (2007) () Resource use and costs Cost of exacerbations CSNS = £154.70 CSS = £178.87 INNOVATE hospitalisation() NHS Reference () PSSRU Unit costs () CSNS=CSS=£213.89 IA-05 EUP() NHS Reference () PSSRU Unit costs () Routine visits 2 per year, £160 each NHS reference costs () 2 per year, £190 each NHS reference costs () Initiation of therapy £245 £247 Standard therapy costs (per year) £1,197 INNOVATE() £810 IA-05 EUP()
Omalizumab costs (per year) £8,056 INNOVATE() £8,455 IA-05 EUP() Administration and monitoring First year: £260 Thereafter: £146 INNOVATE () NHS reference costs () First year: £268 Thereafter: £151 IA-05 EUP () NHS reference costs () S3 Model inputs for maintenance OCS subgroup Adults and adolescents (patients ≥ 12 years) Variables Value Source Baseline annual rate of exacerbations CSNS exacerbations 0.9735 (0.6410 to 1.4784) INNOVATE maintenance OCS () CSS exacerbations 1.000 (0.4493 to 2.2259) INNOVATE maintenance OCS () Proportion of responders 46.94% (32.97% to 60.91%) INNOVATE maintenance OCS () Risk ratio for CSNS exacerbations (responders) 0.4142 (0.1569 to 1.0938) INNOVATE maintenance OCS ()
Risk for CSS exacerbations (responders) 0.2144 (0.0761 to 0.6042) INNOVATE maintenance OCS () Mortality All-cause mortality UK life-tables adjusted for deaths. ONS () deaths mortality rate = 0.4 per 100 person-years De et al (2010) () HRQoL Omalizumab effect on HRQoL HRQoL difference observed in the 0.791 (omalizumab) versus 0.686 (standard care) maintenance OCS() HRQoL loss due to exacerbations CSNS = CSS = -0.20 et al (2007) () Duration of exacerbation 4 weeks Lloyd et al (2007) ()
discontinue OCS Annual acquisition costs of OCS £99.45 per patient EXALT () Costs due to adverse effects of OCS £205.60 Manufacturer submission () Health losses due to adverse effects of OCS 0.02331 DALYs Manufacturer submission () 95%CI – 95% confidence interval. CSS – clinical significant severe exacerbation; CSNS – clinical significant non-severe exacerbation. Table S4 Model inputs for ≥ 3 exacerbations subgroup Adults and adolescents (patients ≥ 12 years) Children (patients 6-11 years) Variables Value Source Value Source Baseline annual rate of exacerbations CSNS exacerbations 2.2143 (1.8070 to 2.7133) INNOVATE≥3 exacerbations () 2.7651 (2.1763 to 3.5132) IA-05 EUP ≥3 exacerbations ()
S5 Full cost-effectiveness results for overall and subgroup populations under the PAS price Population Intervention Mean (£) Mean QALYs ICER (£/QALY) Overall patient population Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 33,153 13.66 Omalizumab 60,406 14.14 57,557 Children (6-11 of age) – age at model entry: 9 years Standard care 40,575 16.72 Omalizumab 76,386 17.39 53,348 Hospitalisation Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 36,531 11.83 Omalizumab 63,410 12.68 31,782 Children (6-11 years of age) – age at model entry: 9 years Standard care 44,871 14.45 Omalizumab 70,967 15.32 30,109
Omalizumab 80,797 16.58 48,537 Table S6 Full cost-effectiveness results for overall and subgroup populations under the list price Population Intervention Mean costs (£) Mean QALYs ICER (£/QALY) Overall patient population Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 33,218 13.66 Omalizumab 72,938 14.13 83,822 Children (6-11 years of age) – age at model entry: 9 years
Standard care 40,218 16.72 Omalizumab 92,497 17.39 78,009 Hospitalisation Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 36,449 11.83 Omalizumab 75,826 12.68 46,431 Children (6-11 years of age) – age at model entry: 9 years Standard care 44,718 14.45 Omalizumab 83,145 15.32 44,142 Maintenance OCS Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 35,902 12.78
Omalizumab 68,995 13.44 50,181 ≥ 3 exacerbations Adults and adolescents (≥ 12 years of age) – age at model entry: 43 years Standard care 36,582 12.92 Omalizumab 69,317 13.34 77,868 Children (6-11 years of age) – age at model entry: 9 years Standard care 42,704 16.04 Omalizumab 96,611 16.74 76,149