Evaluating the Cost-Effectiveness of Celecoxib versus Ibuprofen and Naproxen in Patients with Osteoarthritis in United Arab Emirates Based on the PRECISION Trial

Figures & data

Figure 1 Schematic of Markov model used in the study.

Table 1 Relative Safety Estimates on Osteoarthritis Patients in the PRECISION Trial (Panel A) and Calculated Sub- Component AE Weights (Panel B)

Panel A
Relative Safety Estimates on Osteoarthritis Patients in the PRECISION Trial*
Population		Safety Outcome		Ibuprofen vs Celecoxib HR (95% CI)			Naproxen vs Celecoxib HR (95% CI)
Intention-to-Treat – OA patients in PRECISION^Citation7		MACE domain		1.19 (1.01–1.39)			1.06 (0.91–1.25)
		Serious GI domain		1.47 (1.10–1.96)			1.37 (1.02–1.82)
		Renal domain		1.72 (1.22–2.50)			1.30 (0.89–1.89)
Panel B
Breakdown of AE Domain by Sub-Component AEs^^
MACE Domain Non-fatal Events in PRECISION^Citation6			Serious GI Domain in PRECISION^Citation28			Renal Domain in PRECISION^Citation29
Sub-Component Adverse Event	Weight		Sub-Component Adverse Event		Weight	Sub-Component Adverse Event		Weight
Non-fatal MI	19.9%		Hemorrhage/obstruction/perforation		32.1%	Verified renal insufficiency or failure		53.6%
Non-fatal stroke	12.6%		Symptomatic ulcer		17.6%	Hospitalization for acute renal failure		37.8%
Hospitalization for unstable angina	15.6%		Iron-deficiency anemia of GI origin		50.2%	Hemodialysis or peritoneal dialysis		8.6%
Revascularization	46.8%		–		–	–		–
Hospitalization for TIA	5.2%		–		–	–		–

Notes: *For descriptive purposes only; the actual data used for the model is shown in Supplemental Table S4. ^As in PRECISION each of the three AE domains represent composite toxicity outcomes of other sub-component AEs, parameters on cost, excess mortality, and utilities tied to the composite AE domains were calculated based on the weighted average of the incident rates of the sub-component AEs. Abbreviations: HR, hazard ratio; CI, confidence interval.

Table 2 Cost Model Parameters

Monthly Treatment Acquisition Costs for Average Daily Dose*	Cost
Celecoxib 200 mg	$26.98
Ibuprofen 2050 mg	$20.25
Naproxen 850 mg	$20.50
Cost per Adverse Event**
MACE - Weighted Average	$6834.73	Weights^Citation6 from Table 1
Non-fatal myocardial infarction	$8885.56	19.9%
Non-fatal stroke	$4670.30	12.6%
Hospitalization for unstable angina	$3738.42	15.6%
Revascularization	$8057.22	46.8%
Hospitalization for transient ischemic attack	$2490.46	5.2%
Serious GI Complications – Weighted Average	$1502.48	Weights^Citation28 from Table 1
Gastrointestinal hemorrhage, obstruction, perforation	$4046.84	32.0%
Symptomatic ulcer	$479.78	18.0%
Iron deficiency anemia of GI origin	$234.33	50.0%
Renal Events - Weighted Average	$2436.09	Weights^Citation29 from Table 1
Verified renal insufficiency or failure	$1282.85	53.9%
Hospitalization for acute renal failure	$4152.07	37.2%
Initiation of hemodialysis or peritoneal dialysis	$2080.60	8.9%

Notes: *Source accessed August 2019. Median monthly drug cost calculated based on data from Dubai Health Authority. Drug Lists. Available from: https://www.dha.gov.ae/en/HealthRegulation/Pages/druglist.aspx.⁴⁷ **As in PRECISION each of the three AE domains represent composite toxicity outcomes of other sub-component AEs, parameters on cost tied to the composite AE domains were calculated based on the weighted average of the incident rates of the sub-component AEs.

Table 3 Utility and Excess Mortality Model Parameters*

	Utility		Excess Mortality
	During AE State	Post AE State	During AE State**	Post AE State	Comment
MACE - weighted average	0.618	0.844	Celecoxib:10.4%^Citation6	3.44%
CV related mortality	0	0
Non-fatal myocardial infarction	0.370^Citation13	0.878^Citation13		4.32%^Citation30
Non-fatal stroke	0.350^Citation13	0.708^Citation13	Ibuprofen:12.4%^Citation6	1.69%^Citation31
Hospitalization for unstable angina	0.660^Citation32	0.847^Citation33		2.16%^Citation34	Post AE: Assume half of myocardial infarction^Citation34
Revascularization	0.780^Citation32	0.858^Citation32	Naproxen:14.5%^Citation6	4.32%^Citation35	Post AE: Assume similar to myocardial infarction^Citation35
Hospitalization for transient ischemic attack	0.640^Citation36	0.900^Citation37		0.19%^Citation38	Post AE: Assume 0.10 times higher than background mortality^Citation38
Serious GI complications – weighted average	0.692	0.989	1.38%	0.36%
Gastrointestinal hemorrhage, obstruction, perforation	0.460^Citation39	0.978^Citation13	4.30%^Citation39	1.11%^Citation39
Symptomatic ulcer	0.550^Citation39	0.978^Citation13	0.00%^Citation13	0.00%^Citation13
Iron deficiency anemia of GI origin	0.890^Citation40	1.000	0.00%	0.00%
Renal events - weighted average	0.410	0.785	5.81%	3.73%
Verified renal insufficiency or failure	0.680^Citation41	0.900^Citation42	1.26%^Citation43	0.62%^Citation43	During and post AE: assume 0.67 and 0.33 times higher than background mortality, respectively^Citation43
Hospitalization for acute renal failure	0^Citation44	0.680^Citation41	9.07%^Citation45	4.47%^Citation43	Post AE: Assume 2.38 times higher than background mortality^Citation43
Initiation of hemodialysis or peritoneal dialysis	0.525^Citation42	0.525^Citation42	19.86%^Citation46	19.86%^Citation46	Assume 10.6 times higher than background mortality^Citation46

Notes: *As in PRECISION each of the three AE domains represent composite toxicity outcomes of other sub-component AEs, parameters on cost, excess mortality, and utilities tied to the composite AE domains were calculated based on the weighted average of the incident rates of the sub-component AEs; **For MACE, CV-related death is already a component of the MACE definition and therefore death from that model state was modelled directly as the proportional contribution of the CV-related death as part of the composite MACE domain.

Table 4 Model Results – Cumulative Outcomes and Cost per Patient

Cumulative Outcomes and Costs per Patient Over 30-Month Horizon
	Celecoxib	Ibuprofen	Naproxen	Δ Celecoxib vs Ibuprofen	Δ Celecoxib vs Naproxen
Total LYs	2.3844	2.3814	2.3816	Δ 0.0030	Δ 0.0028
Total QALYs	1.3386	1.3354	1.3366	Δ 0.0033	Δ 0.0021
Total Average Cost	$812.88	$775.26	$731.17	Δ $37.62	Δ $81.71
Drug acquisition costs	$452.63	$336.96	$342.57	Δ $115.67	Δ $110.05
Toxicities costs	$360.25	$438.30	$388.60	Δ -$78.05	Δ -$28.35
MACE costs	$293.77	$346.38	$310.03	Δ -$52.61	Δ -$16.26
GI costs	$16.45	$23.96	$22.44	Δ -$7.51	Δ -$5.99
Renal costs	$15.67	$26.71	$20.29	Δ -$11.04	Δ-$4.61
Post MACE costs	$30.71	$35.49	$30.98	Δ-$4.79	Δ -$0.27
Post GI costs	$1.94	$2.83	$2.64	Δ -$0.89	Δ -$0.71
Post Renal costs	$1.71	$2.93	$2.22	Δ-$1.22	Δ -$0.51
ICER for LYs				$12,676	$29,092
ICER for QALYs				$11,502	$39,779

Note: Δ – difference in.

Abbreviation: LYs, life years; QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio.

Figure 2 Tornado diagrams on deterministic sensitivity analyses: celecoxib vs ibuprofen (top) and vs naproxen (bottom).

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