The cost-effectiveness of a bimekizumab versus IL-17A inhibitors treatment-pathway in patients with active axial spondyloarthritis in Scotland

Figures & data

Table 1. Cost-effectiveness model design and settings.

Parameter	Model setting	Source/rationale
Structure/design	Year 1: decision tree representing treatment-pathway	Real practice assessment of response to bDMARD (L1, L2)
	Year 2 onwards: lifetime Markov model (12-week cycle)	Chronic disease requiring life-time management. Cycle length in line with assessment of response after induction.
	Events and transitions occurring in mid-cycle	Half-cycle correction using life table method.
Mortality	Mortality rate q(x) of general population by age and sex	Life table UK 2018–2020
	Gompertz-Makeham fitting	Golubev^51. MortalityLaw package of R software
	SMR vs. general population (male 1.63, female 1.38)	Bakland et al.^52
Annual discontinuation rate	11% for any cause while on maintenance	TA383
	Of which 50% due to loss of efficacy and 50% due to other cause	Assumption based on trial observations + Glintborg et al.^74
	Initial responders discontinuing between wk 16–52: assuming mean exposure of 39 weeks	BE MOBILE trial
Clinical score change upon treatment discontinuation	Discontinuation due to LoE associated with a rebound equal to 50% of initial improvement.	According to definition of lack of efficacy
	Discontinuation due to other cause associated with a rebound equal to 25% of initial improvement.
Longer term disease progression	BASFI annual worsening rate 0.7%–1.2% while on CC	TA383 / OASIS (prorated to baseline BASFI in BE MOBILE 1 and 2)
	Reduced BASFI worsening rate (0.42) when on any DMARD	Haroon et al.^80
HRQoL: utility estimation	ASDAS mapping to EQ-5D-3L	Alava et al.^60
	Utility scores estimated with the mapping at usual ASDAS cut-off levels^81:
	Active disease (score 3.5+): 0.493
	Low disease activity (score < 2.1): 0.708
	Inactive disease (score < 1.3): 0.820
	Estimated for a population aged 40 years-old, 63% male.
Disease management costs	Visits per quarter, Lab tests per quarter	TA383
	BASFI-based equation for disease management cost: £1450 x exp(0.213 x BASFI)	TA383, constant term inflated from 2016 to 2022
Treatment-pathways	BKZ: bimekizumab 160 mg → TNFi → BSC	SmPC + ASAS/EULAR guidelines
	SEC: secukinumab 150 mg → TNFi 43%, secukinumab 300 mg 57% blended line → BSC	SmPC + ASAS/EULAR guidelines + registry reuma.pt
	IXE: ixekizumab 80 mg → TNFi → BSC	SmPC + ASAS/EULAR guidelines
% of DMARD in BSC	87%	Scotland advisory board
Perspective	NHS Scotland (direct medical costs)	SMC guidelines
Discount rate	3.50% per year for costs and outcomes	SMC guidelines
WTP	£30,000 per QALY gained	Assumption
Baseline patients characteristics	nr-axSpA	r-axSpA
Sex, % male	54.3%	72.3%
Age (years), mean (SD)	39.4 (11.6)	40.4 (12.3)
ASDAS, mean (SD)	3.7 (0.7)	3.7 (0.8)
BASFI, mean (SD)	5.4 (2.3)	5.2 (2.1)
Prior TNFi exposure, % yes	10.6%	16.3%

Abbreviations. ASAS, Assessment of SpondyloArthritis international Society; ASDAS, Axial Spondyloarthritis Disease Activity Score with C-reactive protein; axSpA, axial spondyloarthritis; BASFI, Bath Ankylosing Spondylitis Functional Index; BSC, best supportive care; (b)DMARD, (biologic-)disease-modifying antirheumatic drug; EULAR, European Alliance of Associations for Rheumatology; HRQoL, health-related quality of life; lL1, first-line; L2, second-line; NHS, National Health Service; nr, non-radiographic; SD, standard deviation; SMC, Scottish Medicine Consortium; SmPC, summary of product characteristics; TNFi, tumor necrosis factor-alpha inhibitor; WTP, willingness-to-pay.

Figure 1. AxSpA treatment-pathways applied in the model. AxSpA treatment-pathways applied in the model were defined in line with ASAS/EULAR and SmPC recommendations. In Line 2, TNFi were taken as a class, with efficacy data from an SLR/NMA and cost data based on individual TNFi list prices weighted by their estimated market shares in Scotland. ASAS, Assessment in Spondyloarthritis international Society; BSC, best supportive care; BKZ, bimekizumab treatment-pathway; b/ts, biologic/targeted synthetic; DMARD, disease modifying antirheumatic drug; EULAR, European League Against Rheumatism; IL, interleukin; IXE, ixekizumab treatment-pathway; nr-/r-axSpA, non-radiographic/radiographic axial spondyloarthritis; SEC, secukinumab treatment-pathway; SmPC, summary of product characteristics; TNFi, tumor necrosis factor-alpha inhibitor.

Figure 2. Model structure: decision tree for first year treatment-pathway. Patients with active axSpA start a treatment-pathway with a first b/tsDMARD (L1). At the end of the initial 16-week assessment period, their clinical response is evaluated: (a) BASDAI50 responders continue initial treatment L1; a proportion of L1 responders will however discontinue L1 between w17 and w52 (any cause discontinuation, assumed to occur at an annual rate of 11%). After L1 discontinuation, patients get a next b/tsDMARD treatment (L2) which is assumed to start with the Markov model as from year 2. (b) BASDAI50 non responders stop initial treatment L1 and start a next b/tsDMARD treatment (L2) for another 16-week assessment period (or 12 weeks if L2 is a TNFi) with clinical response evaluation: BASDAI50 responders start L2 maintenance treatment, subject to a 11% annual discontinuation rate for any cause between w28 and w52, after which they receive BSC. BASDAI50 non-responders stop L2 treatment and receive BSC from w28 onwards until the end of the first year. The treatment-pathways modeled for one year determine the initial health states distribution for the Markov model. No discontinuation was assumed to occur during an assessment period (week 1–16 for L1, and week 17–28 for L2). axSpA, axial spondyloarthritis; BSC, best supportive care; L1/2, line 1/2; resp., response; Tx, treatment.

Figure 3. Model structure: Markov model as from second year of treatment until death. Initial distribution determined by outcome of decision tree. Three-month Markov cycles until end of horizon (or death). BSC, best supportive care; disc, discontinuation; L1/2, biologic line 1/2; resp, responder.

Table 2. Efficacy and safety data inputs.

Endpoint at week 12–16	nr-axSpA		r-axSpA
BASDAI50 response^a	Absolute rate	RR vs. BKZ (95% CrI)	Absolute rate	RR vs. BKZ (95% CrI)
Bimekizumab	0.451 (0.312, 0.604)		0.4130 (0.33, 0.51)
Conventional care	0.198	0.44 (0.33, 0.62)	0.169	0.41 (0.34, 0.50)
Secukinumab	0.361	0.80 (0.52, 1.21)	0.314	0.76 (0.55, 1.08)
Ixekizumab	0.415	0.92 (0.53, 1.49)	0.446	1.08 (0.75, 1.51)
Upadacitinib	0.388	0.86 (0.57, 1.33)	0.413	1.00 (0.71, 1.37)
TNFi class sc	0.469	1.04 (0.75, 1.49)	0.483	1.17 (0.98, 1.46)
ASDAS CfB^b	Absolute CfB	DCfB vs. BKZ (95% CrI)	Absolute CfB	DCfB vs. BKZ (95% CrI)
Bimekizumab	−1.42 (−1.68, −1.16)		−1.38 (−1.88, −0.94)
Conventional care	−0.56	0.86 (0.62, 1.11)	−0.52	0.86 (0.43, 1.35)
Secukinumab	−1.11	0.31 (−0.02, 0.64)	−1.18	0.20 (−0.44, 0.86)
Ixekizumab	−1.11	0.31 (−0.06, 0.68)	−1.63	−0.25 (−0.95, 0.49)
Upadacitinib	−1.21	0.21 (−0.17, 0.59)	−1.46	−0.08 (−0.81, 0.76)
TNFi class sc	−1.52	−0.10 (−0.39, 0.19)	−1.68	−0.30 (−0.72, 0.13)
Stratification by response^c	Ratio CfB R:NR BASDAI50	Source	Ratio CfB R:NR BASDAI50	Source
bDMARD	3.11	BE MOBILE 1 post-hoc	2.38	BE MOBILE 2 post-hoc
Conventional care	4.53		3.23
Long-term evolution	Constant		Constant
BASFI CfB^a	Absolute CfB	DCfB vs. BKZ (95% CrI)	Absolute CfB	DCfB vs. BKZ (95% CrI)
Bimekizumab	−2.44 (−3.03, −1.89)		−1.84 (−2.20, −1.45)
Conventional care	−0.90	1.54 (1.04, 2.11)	−0.61	1.23 (0.91, 1.53)
Secukinumab	−1.65	0.79 (0.04, 1.58)	−2.30	−0.46 (−1.12, 0.16)
Ixekizumab	−1.58	0.86 (0.08, 1.71)	−1.75	0.09 (−0.39, 0.57)
Upadacitinib	−2.04	0.40 (−0.46, 1.24)	−1.93	−0.09 (−0.68, 0.50)
TNFi class	−2.24	0.20 (−0.42, 0.82)	−1.96	−0.12 (−0.49, 0.23)
Stratification by response^c	Ratio CfB R:NR BASDAI50		Ratio CfB R:NR BASDAI50
bDMARD	3.817		2.680
Conventional care	5.180		4.439
Long-term evolution	BASFI +0.7% per year		BASFI +1.2% per year
Safety (axSpA)
Rate per 100 person-years	Serious infection	Tuberculosis reactivation	Source
Bimekizumab	2 (1.12)	0 (0)	BE MOBILE 1 and 2
Conventional care	0 (0)	0 (0)	Assumption
Secukinumab	1.5 (0.48)	0 (0)	TA718
Ixekizumab	1.5 (0.48)	0 (0)	TA718
Upadacitinib	4.1 (0.48)	0 (0)	SmPC
TNFi class sc	3.87 (0.48)	0.16 (0.02)	TA383

Notes: For each NMA endpoint, the best fit model according to AIC criteria was retained as model input (Fixed Effects without adjustment for nr-axSpA, Fixed or Random Effects with adjustment to placebo for r-axSpA).

Abbreviations. BASDAI50, Bath Ankylosing Spondylitis Disease Activity Index 50% improvement; BASFI, Bath ankylosing spondylitis functional index; NR, non-responder; R, responder; RR, relative risk; sc, subcutaneous; SmPC, summary of product characteristics; TA, technology appraisal; TNFi, tumor necrosis factor-alpha inhibitor.

^aBASDAI50 and BASFI results were provided by PREVENT (nr-axSpA) and MEASURE 2 (r-axSpA) trials for secukinumab^82,83 and by COAST-X (nr-axSpA) and COAST-V (r-axSpA) trials for ixekizumab.^84,85

^bASDAS results were provided by PREVENT (nr-axSpA) and MEASURE 2, ASTRUM (r-axSpA) trials for secukinumab^82,83,86 and by COAST-X (nr-axSpA) and COAST-V, Xue 2022 (r-axSpA) trials for ixekizumab^84,85,87.

^cThe ratio (Ratio_{_R:NR}) was estimated from post-hoc analyses of BE MOBILE 1 and 2 trial data, and applied in the model in a way that maintains consistency between response rate (pctR) and overall CfB (CfBScore_{_All}) at week 16 at treatment level:.

(1) CfBScore_{_NR} = CfBScore_{_All}/[(Ratio_{_R:NR} – 1) x pctR + 1].

(2) CfBScore_{_R} = CfBScore_{_NR} x Ratio_{_R:NR}.

Table 3. Healthcare resource use and cost inputs.

Medications	Schedule	Acquisition cost (£)		Administration cost (£)^a
Comparator	Induction (if any) Maintenance	Induction	Maintenance (per year)	Induction	Maintenance (per year)
Bimekizumab	160 mg Q4W	0	15,934.03	46.00	0
Conventional care	Daily	0	25.90	0	0
Adalimumab	40 mg Q2W	0	3,536.14	46.00	0
Etanercept	50 mg QW4	0	8,394.23	46.00	0
Golimumab sc	50 mg once monthly	0	9,155.64	46	0
Infliximab	5 mg/kg at W0, 2, and 6 Maintenance every 6 weeks	4,575.46	9,947.54	860.51	2,129.28
Secukinumab 150	160 mg loading dose w0, 1, 2, 3, 4 Maintenance 160 mg once monthly	3,046.95	7,312.68	46.00	0
Certolizumab pegol	400 mg at W0, 2 and 4 Maintenance 200 mg Q2W or 400 mg Q4W2	2,145.00	9,326.92	46.00	0
Ixekizumab	80 mg Q4W	2,250.00	14,675.22	46.00	0
Upadacitinib	15 mg daily	0	10,508.24	0	0
Secukinumab 300	300 mg once monthly	0.00	14,625.36	46.00	0
TNFi class sc	Weighted average	265.36	6,447.24	46.00	0
HRU (all bDMARD comparators)	axSpA routine monitoring	Rheumatologist visits (£)		Laboratory tests (£)
Source	As per York model	Induction	Maintenance	Induction	Maintenance
Cost per quarter	(costing year 2022)	460.76	94.08	233.71	13.81

^a1-h of patient-related nurse time for subcutaneous products. This cost was applied once per treatment line, at start of the induction phase.

Figure 4. Multiple CEAC bimekizumab treatment-pathway vs. IL-17Ai treatment-pathways (axSpA population). BKZ and SEC cross at WTP £26,000 (probability of being cost-effective 33%). BKZ and IXE cross at WTP £31,000 (probability of being cost-effective 38%). Error bars indicate 95% confidence interval around the probability of being cost-effective. BKZ, bimekizumab treatment-pathway; CEAC, cost-effectiveness acceptability curve; IL, interleukin; IXE, ixekizumab treatment-pathway; nr-/r-axSpA, non-radiographic/radiographic axial spondyloarthritis; SEC, secukinumab treatment-pathway; WTP, willingness-to-pay.

Table 4. Probabilistic base case, fully incremental cost-effectiveness results in axSpA population.

Fully incremental analysis	Probabilistic base case, axSpA population
Tx-pathway	Cost	QALY	Incr cost (£)	Incr QALY	ICER (£/QALYs)	NMB (£)
SEC	198,073	10.897	–	–	–	–
IXE	213,081	11.448	Str dom	Str dom	Str dom	Str dom
BKZ	212,696	11.487	14,623	0.590	24,801	3,065

Note: Results per indication (nr-axSpA, r-axSpA) shown in supplement S3.

Abbreviations. axSpA, axial spondyloarthritis; BKZ, bimekizumab treatment-pathway; ICER, incremental cost-effectiveness ratio; incr, incremental; IXE, ixekizumab treatment-pathway; NMB, net monetary benefit; nr, non-radiographic; QALY, quality-adjusted life-years; SEC, secukinumab treatment-pathway; Ext: extendedly dominated; Str dom, strongly dominated Tx, treatment.

Table 5. Probabilistic base case, pairwise cost-effectiveness results in combined axSpA population.

Pairwise comparison	Probabilistic base case, axSpA population
	Incr cost (£)		Incr QALY		ICER (£/QALY)		NMB (£)
Tx-pathway	Mean	95% CrI	Mean	95% CrI	Mean	95% CrI	Mean	95% CrI
BKZ vs. SEC	14,623	(5,829; 23,418)	0.590	(−0.048; 1.227)	24,801	(23,972; 25,690)	3,065	(2,453; 3,677)
BKZ vs. IXE	−385	(−15,239; 14,468)	0.039	(−0.748; 0.825)	Dominant	Dominant	1,542	(862; 2,222)
IXE vs. SEC	15,008	(−272; 30,289)	0.551	(−0.392; 1.494)	27,236	(26,062; 28,521)	1,523	(779; 2,268)

Note: Results per indication (nr-axSpA, r-axSpA) shown in supplement S3.

Abbreviations. axSpA, axial spondyloarthritis; BKZ, bimekizumab treatment-pathway; CrI: credible interval; ICER, incremental cost-effectiveness ratio; incr, incremental; IXE, ixekizumab treatment-pathway; NMB, net monetary benefit; nr, non-radiographic; QALY, quality-adjusted life-years; SEC, secukinumab treatment-pathway; Ext: extendedly dominated; Str dom, strongly dominated Tx, treatment.

Figure 5. DSA BKZ vs. SEC (axSpA).

Figure 6. DSA BKZ vs. IXE (axSpA). NMB ranges obtained by applying the variations around the deterministic base case NMB to the probabilistic base case NMB. axSpA, axial spondyloarthritis; BASFI, Bath Ankylosing Spondylitis Functional Index; BKZ, bimekizumab treatment-pathway; NMB, net monetary benefit; nr, non-radiographic; trt, treatment; RR, relative risk.

Table 6. Probabilistic scenarios analyses, axSpA population.

Fully incremental analysis	Probabilistic results of scenario analyses
Tx-pathway	Cost (£)	QALY	Incr cost (£)	Incr QALY	ICER (£/QALYs)	NMB (£)
ASAS40 response criteria
SEC	198,148	10.948	–	–	–	–
IXE	213,762	11.511	Str dom	Str dom	Str dom	Str dom
BKZ	213,374	11.542	15,226	0.594	25,614	2,607
47% up-titration to secukinumab 300 mg
SEC	196,184	10.952	–	–	–	–
IXE	213,081	11.448	Str dom	Str dom	Str dom	Str dom
BKZ	212,696	11.487	16,512	0.534	30,894	−478
JAKi in second-line
SEC	200,129	10.832	–	–	–	–
IXE	218,620	11.304	Str dom	Str dom	Str dom	Str dom
BKZ	218,358	11.340	18,228	0.508	35,907	−2,999

Abbreviations. axSpA, axial spondyloarthritis; BKZ, bimekizumab treatment-pathway; ICER, incremental cost-effectiveness ratio; incr, incremental; IXE, ixekizumab treatment-pathway; NMB, net monetary benefit; nr, non-radiographic; QALY, quality-adjusted life-years; SEC, secukinumab treatment-pathway; Ext: extendedly dominated; Str dom, strongly dominated Tx, treatment.

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