Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK

Figures & data

Figure 1. Clinical pathway of care for treatment of acute migraine. Abbreviations. AEs, adverse events; BSC, best supportive care; NSAIDs, non-steroidal anti-inflammatory drugs. ¹Consider an anti-emetic in addition to other acute treatment for migraine even in the absence of nausea and vomiting. ²When prescribing a triptan, start with the one with the lowest acquisition cost. Adapted from NICE CG150.

Table 1. Features of rimegepant acute treatment migraine model structure.

	Description	Rationale
Type of model	Decision tree plus Markov model	There have been no previous TAs in the acute treatment of migraine, but this model structure was informed by a US analysis (Atlas et al.^44)
Cycle length	48 h	Typical duration of clinical trials evaluating acute migraine treatments and clinical duration of migraine events^45.
Discount rate	3.5% per year	NICE reference case^46
Half-cycle correction	No	Given a cycle length of 2 days, it is anticipated that a half-cycle correction would have negligible results.
Comparator	BSC	Given positioning of rimegepant for ≥2 triptan discontinuers, no effective alternatives exist.

Abbreviations. BSC, best supportive care; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; PSS, Personal Social Services; TA, technology appraisal; UK, United Kingdom; US, United States.

Figure 2. Overview of the model structure for acute treatment of migraine. *Background mortality included as a separate state.

Table 2. Summary of model inputs, settings, and rationale.

Variable	Base case value	Source	Rationale
Time horizon	Lifetime (20 years)	NICE reference case^46 given migraine is a chronic condition	Despite the peak in prevalence in working aged individuals, migraine impact patients over the course of their lifetime^54–57. A 20 year time horizon was further supported by the rimegepant trial demographics^51^,^58^,^59 clinician insights, and patient testimonial^60.
Population used for efficacy estimation	≥2 triptan discontinuer population	Pooled BHV3000-301, 302, 303^51^,^58^,^59	Representative of the target population.
Population used for baseline characteristics	≥2 triptan discontinuer population	BHV3000-201^41	The BHV3000-201 trial was used as the source of clinical characteristics as the acute trials (BHV3000-301, −302, and −303) restricted inclusion on the number of migraine attacks per month from 2 to a maximum of 8, whilst the BHV3000-201 trial did not have this restriction and better represents the migraine population in clinical practice.
Probability of experiencing migraine	Calculated based on baseline MMD frequency distribution	Open-label long-term safety study (BHV3000-201)^42	The rimegepant phase 3 acute trials (BHV3000-301, −302, and −303) restricted inclusion to two to eight migraine attacks per month, and thus do not provide a natural distribution of the full range of MMD potentially observed in the UK population. Therefore, the baseline MMD data from BHV3000-201 trial were used.
Pain trajectories	Modelled using regression analysis	Post-hoc pooled phase 3 acute treatment trials^41	Efficacy measured using subjects who are representative of the target population (≥2 triptan discontinuers). Regression analysis accounted for key covariates including age, sex, baseline MMD, and baseline pain severity.
Discontinuation rate of rimegepant	9.7% per year^a	≥2 triptan discontinuers from BHV3000-201 Open-label long-term safety study (BHV3000-201)^42	Informed by rimegepant discontinuations in a 52-week open label study, as this was deemed to be the best estimate for discontinuation in clinical practice.
Reduction in MMD frequency	Modelled using regression analysis	Open-label long-term safety study (BHV3000-201)^42	Repeated acute use of rimegepant PRN has been observed to have a preventive impact^43^,^61.
Waning of BSC (placebo) response	BSC responders will transition to BSC non-responder trajectories after 12 months	Supported by clinical experts.	This was among the preferred assumptions for fremanezumab technology appraisal^50, and was supported by clinical experts.
Response rate (pain relief at 2 h)	Rimegepant: 69.6% BSC: 36.7%	Post-hoc pooled phase 3 acute treatment trials^41	Pain relief at 2 h is deemed to be both clinically relevant and of importance to patients, was supported by clinical expert feedback.
Utility at baseline and during non-migraine cycles	0.72	Patient-level MSQv2 data from BHV3000-201 mapped to EQ-5D-3L utility scores using algorithm from Gillard et al.^62	Aligned with utility mapping methodology used in previous technology appraisals in migraine^49^,^50^,^63.
Utility by pain severity	Severe: −0.20 Moderate: 0.53 Mild: 0.66 None: 0.87	Stafford et al. 2014^64	Stafford et al. was a cross-sectional observational study conducted in the UK and used the UK population scoring algorithm when calculating pain state utility values. It was deemed the relevant source measured in UK patients, which was supported by clinical expert feedback. The utility values from Stafford et al. were adjusted in order to retain the differences across pain categories, while reflecting the expectation that time periods without a migraine will have better HRQoL than time periods with a migraine
Event utility	0.0054 utility increment per MMD averted	Utilities from Stafford et al.^64 were adjusted to ensure that pain-free utility was equivalent to non-migraine MSQv2-mapped utility value, and values for other categories were adjusted accordingly
All-cause mortality	Age- and sex-specific UK life tables	Office for National Statistics^53	No excess mortality is thought to be associated with migraine, therefore patients in all model states have an equal risk of transitioning to death, which was based on UK life tables. This is consistent with prior NICE TAs in migraine^49^,^50^,^63.
Probability of HCRU	Hospitalization: 0.003 ED: 0.010 GP visit: 0.066	Per-migraine probability of HCRU calculated from Vo et al.^65	This is consistent with prior NICE TAs in migraine^49^,^50^,^63.
Drug acquisition cost	£103.20 per 8-pack for rimegepant	BNF^66^,^67	--
BSC cost	No cost applied	--	Assumed no cost given the placement of rimegepant among ≥2 triptan discontinuer, and no other active therapy options.
Resource unit costs	Hospitalization: £643.29 ED: £188.07 GP visit: £39.23	PSSRU and NHS reference costs^68^,^69	This is consistent with prior technology appraisals in migraine^49^,^50^,^63.

Abbreviations. BNF, British National Formulary; BSC, best supportive care; ED, emergency department; GP, general practitioner; HCRU, health care resource utilization; MMD, monthly migraine days; MSQv2, Migraine-Specific Quality of Life Questionnaire, version 2; NA, not applicable; NHS, National Health Service; PSSRU, Personal Social Services Research Unit; UK, United Kingdom.

^aInformed by discontinuations due to adverse events, lack of efficacy, or withdrawal by subjects from BHV3000-201 study, for subgroup of ≥2 triptan discontinuers.

Table 3. Key assumptions in the acute economic model.

Parameter	Base-case assumption	Justification
Efficacy of rimegepant over time	Constant over time for patients continuing therapy	Limited data available for pain trajectories (single-attack study only), but relatively high retention of patients receiving acute treatment in long-term safety study BHV3000-201 implies ongoing effectiveness. Responder-based analysis assumed that only patients retaining benefit remain on treatment, further justifying assumption of retained benefit for those patients remaining on therapy. In real-world practice, patients losing response are expected to discontinue therapy and no longer incur costs, accounted for with the annual discontinuation rate estimated from BHV3000-201.
Waning of placebo effect	Assumed that BSC responders will transition to BSC non-responder trajectories after 12 months	The dissipation of the placebo effect was included as it was the committees’ preferred assumptions for fremanezumab^50, where the treatment effect for people who responded to BSC diminished to baseline over 1 year. Discussion with experts suggests it was the general understanding that placebo always wanes over time. While it was difficult to come to consensus as views were varied and complex, the pragmatic view is that 12 months is a long time for placebo effect in acute, but a wide range of time period ranging from 6 months to 12 months was also suggested.
Response following rimegepant discontinuation	Assumed to revert to BSC non-responders after 1 year at BSC responder rate	Assumption of parity for BSC responders, who experience 12 months of response prior to reversion to non-response.
Mortality	Assumed to follow general population mortality	Aligns with prior NICE TAs in migraine prevention^49^,^50^,^63 and is supported by a published meta-analysis, which found no association between migraine and all-cause mortality^70.
Effect of rimegepant treatment on monthly migraine frequency	Potential for reduction in MMD frequency based on patient characteristics (including baseline MMD)	As observed in the long-term safety study BHV3000-201, there is evidence of migraine reduction with as-needed acute treatment with rimegepant^43^,^71; further supported by clinical expert panel.

Abbreviations. BSC, best supportive care; MMD, monthly migraine days; NICE, National Institute of Health and Care Excellence; TA, technology appraisal.

Table 4. Baseline patient characteristics, pooled across acute trials of rimegepant and stratified by triptan discontinuation status.

	Study BVH3000-201	Post-hoc pooled acute trials
	≥ 2 triptan discontinuations	mITT	1 triptan discontinuation	≥ 2 triptan discontinuations
Age (years)	45.7	40.2	41.7	43.6
Sex (% female)	90.9	86.3	90.4	92.9
Mean baseline attacks per month	9.2	4.6	4.7	4.7

Abbreviations. mITT, modified intention-to-treat.

Figure 3. Patient pain trajectories for ≥2 triptan discontinuers treated with rimegepant or placebo in Studies BHV3000-301, -302-, 303.

Table 5. Deterministic one-way sensitivity analysis ranges.

Parameter	Base case value	Lower value	Upper value
Responder Yes parameter QALH regression	6.46	4.1	8.82
Rimegepant parameter QALH regression	2.74	0.46	5.03
MMD parameter QALH regression	−0.68	−1.27	−0.1
Baseline MMD	9.2	7.36	11.04
Moderate/severe 24 h per migraine, BSC non-responder	0.28	0.16	0.41
Age	45.7	18	65
Intercept QALH regression	34.05	30.55	37.54
EQ-5D regression: intercept	0.71	0.7	0.73
EQ-5D regression: age covariate	0.001	0.006	0.0014
Rimegepant discontinuation per year	0.1	0.02	0.22

Abbreviations. BSC, best supportive care; EQ-5D, EuroQoL-5D; hr, hour; MMD, monthly migraine days; QALH, quality-adjusted life hour.

Table 6. Base-case results acute treatment of migraine.

Treatment	Total costs (£)	Total QALYs	Incremental costs (£)	Incremental QALYs	ICUR (£/QALY)
Weighted across MMD distribution observed in Study BHV3000-201 (≥ 2 triptan discontinuation group)
Rimegepant	6,769	8.01	4,492	0.44	10,309
BSC	2,277	7.58

Abbreviations. BSC, best supportive care; ICUR, incremental cost-utility ratio; MMD, monthly migraine days; QALYs, quality-adjusted life years.

Figure 4. Cost-effectiveness acceptability curves for rimegepant and best supportive care.

Table 7. Results of the probabilistic sensitivity analysis for rimegepant vs best supportive care for the acute treatment of migraine.

Treatment	Total costs (£)	Total QALYs	Incremental costs (£)	Incremental QALYs	ICUR (£/QALY)
Rimegepant	6,767	8.01	4,497	0.44	10,337
BSC	2,270	7.58

Abbreviations. BSC, best supportive care; ICUR, incremental cost-utility ratio; QALY, quality-adjusted life-year.

Figure 5. Tornado diagram for the deterministic sensitivity analysis of rimegepant vs best supportive care. Abbreviations. EQ-5D, EuroQoL-5D; MMD, monthly migraine days; QALH, quality-adjusted life hour.

Table 8. Scenario analysis: rimegepant vs best supportive care.

Scenario	Description	Base case	Parameter(s) value in scenario	Incremental costs (£)	Incremental QALYs	Incremental cost per QALY (£)
1	Base case	--	--	4,492	0.44	10,309
2	NICE base case	See Table 2	See Supplementary Table 4	1,124	0.04	29,833
3	Discount rate	3.5%	1.5%	5,003	0.49	10,257
4	Time horizon	20 years	2 years	1,211	0.10	12,364
		20 years	5 years	2,433	0.22	10,819
		20 years	10 years	3,616	0.35	10,426
5	Responder definition	Pain relief at 2 h	Pain relief at 8-h	3,970	0.68	5,796
6	Reduction of MMD frequency among frequent PRN rimegepant users	Include	Exclude	5,267	0.38	13,952
7	QALH utility	From regression	Raw data: Pain intensity x hour	4,492	0.45	10,009
8	Event utility regression	Multiplicative adjustment	Additive adjustment	4,492	0.56	7,984
9	Migraine event utility values Pain intensity × hour	Stafford et al.^64 as published	Set severe utility to zero instead of negative value	4,492	0.41	11,049
10	Patient population from pooled rimegepant acute trials	≥2 triptan discontinuations	mITT	4,566	0.43	10,621
11	Rimegepant discontinuation annual rate	Use discontinuation due to AEs, lack of efficacy, or withdrawal by participant from Study BHV3000-201^76 (9.7% annually)	Use “all cause” discontinuation to inform the model (20% annually) from Study BHV3000-201^76	2,574	0.26	10,089
12	Response following rimegepant discontinuation	Assumed to revert to placebo non-responders after one year at placebo responder rate	Immediately revert to BSC non-responders at discontinuation	4,492	0.41	10,884
13	BSC waning effect (time period before BSC responders transition to BSC non-responder trajectories)	12 months	6 months	4,475	0.43	10,306
		12 months	18 months	4,508	0.44	10,305

Abbreviations. AE, adverse event; BSC, best supportive care; mITT, modified intention to treat; MMD, monthly migraine days; NHS, National Health Service; PRN, as needed; PSS, Personal Social Services; QALH, quality-adjusted life hour; QALY, quality adjusted life year.

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