Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Updated cost-effectiveness analysis of onabotulinumtoxinA for the prevention of headache in adults with chronic migraine who have previously received three or more preventive treatments in the UK.

Aims: OnabotulinumtoxinA is recommended by NICE for the treatment of chronic migraine. This economic evaluation provides updated estimates of the cost-effectiveness of onabotulinumtoxinA for chronic migraine using new utility estimates in an existing model structure.Methods: A previously published model was revised to include EQ-5D utility estimates from a large observational study (REPOSE; n = 633). Efficacy data were taken from the pooled phase III PREEMPT clinical trial program, while resource utilization estimates were obtained from the International Burden of Migraine Study (IBMS). The model estimated costs and quality-adjusted life years (QALYs) gained over 2 years from the UK NHS perspective.Results: OnabotulinumtoxinA treatment resulted in total discounted incremental costs of £1,204 and an incremental discounted QALY gain of 0.07 compared with placebo in patients with chronic migraine who have previously failed three or more preventive treatments, corresponding to an incremental cost-effectiveness ratio (ICER) of £16,306 per QALY gained. Scenario analysis showed that the administration of onabotulinumtoxinA by a specialist nurse rather than a neurology consultant reduced the ICER from £16,306 to £13,832 per QALY gained. Removal of the positive stopping rule recommended in current NICE guidance increased the ICER to £20,768 per QALY for onabotulinumtoxinA vs. placebo. Combining these two scenarios produced an ICER of £17,686 per QALY gained.Conclusion: NICE recommended onabotulinumtoxinA for the prevention of chronic migraine in 2012 amid concerns about the uncertainty of ICER estimates, with a positive stopping rule used to manage some of these uncertainties. Since the publication of the NICE guidance, the REPOSE study provides a more recent source of utility data based on real-world evidence. The results of analyses including these utilities suggest that the application of the positive stopping rule may not be necessary to ensure cost-effectiveness and that this aspect of the current NICE guidance for onabotulinumtoxinA may merit reconsideration.

Costs associated with non-medical switching from originator to biosimilar etanercept in patients with rheumatoid arthritis in the UK.

Aims: To estimate the cost impact of non-medical switching from originator to biosimilar etanercept in stable patients with rheumatoid arthritis (RA) in the UK. Materials and methods: A cohort-based decision tree model was developed with a 1-year time horizon. The model population included patients with stable RA (patients who responded to originator etanercept treatment with no treatment changes in the previous 6 months). Patients could undergo a non-medical switch to a biosimilar and then switch treatment again, if medically required, after 3-6 months. Data on the proportion of patients switching therapies, baseline healthcare resource use, and impact of switching on resource use were sourced from a survey of 150 rheumatologists from EU5 markets (France, Germany, Italy, Spain, UK). The average impact of switching was evaluated as mean values for change in resource utilization due to switching. Also, low- and high-impact scenarios (lower and upper values of the 95% confidence intervals for change in resource utilization due to switching) were modelled as sensitivity analyses. Cost data came from published UK sources. Results: The model assumed that 5,000 patients were treated with originator etanercept, with 1,259 (25.2%) switching to a biosimilar. Of those, 875 (69.5%) and 384 (30.5%) switched to SB4 and GP2015, respectively. After 3 months, 26.3% of patients who switched treatments did so again: 8.3% back to originator, 3.8% to the other biosimilar, and 14.2% to another biologic. Although originator etanercept was more expensive than the biosimilars, switching was more costly than continuous originator treatment across all impact scenarios. Switching treatment chains had higher overall annual per-patient costs than continuous originator treatment. Switching was associated with increased healthcare resource use. Limitations: Results from this analysis are not transferable to other (non-RA) etanercept indications. Conclusion: Non-medical switching can result in increased payer costs because of increased healthcare resource use following switching.

Seal or Varnish? A randomised controlled trial to determine the relative cost and effectiveness of pit and fissure sealant and fluoride varnish in preventing dental decay.

BACKGROUND: Fissure sealant (FS) and fluoride varnish (FV) have been shown to be effective in preventing dental caries when tested against a no-treatment control. However, the relative clinical effectiveness and cost-effectiveness of these interventions is unknown. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- and 7-year-olds and to determine their acceptability. DESIGN: A randomised controlled allocation-blinded clinical trial with two parallel arms. SETTING: A targeted population programme using mobile dental clinics (MDCs) in schools located in areas of high social and economic deprivation in South Wales. PARTICIPANTS: In total, 1016 children were randomised, but one parent subsequently withdrew permission and so the analysis was based on 1015 children. The randomisation of participants was stratified by school and balanced for sex and primary dentition baseline caries levels using minimisation in a 1 : 1 ratio for treatments. A random component was added to the minimisation algorithm, such that it was not completely deterministic. Of the participants, 514 were randomised to receive FS and 502 were randomised to receive FV. INTERVENTIONS: Resin-based FS was applied to caries-free FPMs and maintained at 6-monthly intervals. FV was applied at baseline and at 6-month intervals over the course of 3 years. MAIN OUTCOME MEASURES: The proportion of children developing caries into dentine (decayed, missing, filled teeth in permanent dentition, i.e. D4-6MFT) on any one of up to four treated FPMs after 36 months. The assessors were blinded to treatment allocation; however, the presence or absence of FS at assessment would obviously indicate the probable treatment received. Economic measures established the costs and budget impact of FS and FV and the relative cost-effectiveness of these technologies. Qualitative interviews determined the acceptability of the interventions. RESULTS: At 36 months, 835 (82%) children remained in the trial: 417 in the FS arm and 418 in the FV arm. The proportion of children who developed caries into dentine on a least one FPM was lower in the FV arm (73; 17.5%) than in the FS arm (82, 19.6%) [odds ratio (OR) 0.84, 95% confidence interval (CI) 0.59 to 1.21; p = 0.35] but the difference was not statistically significant. The results were similar when the numbers of newly decayed teeth (OR 0.86, 95% CI 0.60 to 1.22) and tooth surfaces (OR 0.85, 95% CI 0.59 to 1.21) were examined. Trial fidelity was high: 95% of participants received five or six of the six scheduled treatments. Between 74% and 93% of sealants (upper and lower teeth) were intact at 36 months. The costs of the two technologies showed a small but statistically significant difference; the mean cost to the NHS (including intervention costs) per child was £500 for FS, compared with £432 for FV, a difference of £68.13 (95% CI £5.63 to £130.63; p = 0.033) in favour of FV. The budget impact analysis suggests that there is a cost saving of £68.13 (95% CI £5.63 to £130.63; p = 0.033) per child treated if using FV compared with the application of FS over this time period. An acceptability score completed by the children immediately after treatment and subsequent interviews demonstrated that both interventions were acceptable to the children. No adverse effects were reported. LIMITATIONS: There are no important limitations to this study. CONCLUSIONS: In a community oral health programme utilising MDCs and targeted at children with high caries risk, the twice-yearly application of FV resulted in caries prevention that is not significantly different from that obtained by applying and maintaining FSs after 36 months. FV proved less expensive. FUTURE WORK: The clinical effectiveness and cost-effectiveness of FS and FV following the cessation of active intervention merits investigation. TRIAL REGISTRATION: EudraCT number 2010-023476-23, Current Controlled Trials ISRCTN17029222 and UKCRN reference 9273. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 21. See the NIHR Journals Library website for further project information.