Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that affects the axial skeleton, causing characteristics inflammatory back pain, which can lead to structural and functional impairments. Asymmetric peripheral arthritis is present in about 20–40% of patients with AS [
The first-line treatment of AS is nonsteroidal anti-inflammatory drugs (NSAIDs) [
Given the economic burden of AS, a cost-effectiveness analysis of interventions for AS is warranted. The objective of this study was to evaluate the cost-effectiveness of etoricoxib (90 mg) compared to celecoxib (200 and 400 mg), diclofenac (150 mg), and naproxen (1000 mg) in the treatment of patients with AS in Norway. Analyses were performed from the health care perspective.
In the present economic evaluation, a comprehensive decision Bayesian modelling approach was used which integrates evidence synthesis and parameter estimation for efficacy and safety with cost-effectiveness modeling in a single unified framework [
A previously published Markov-state transition model was used to estimate the cost-effectiveness of etoricoxib versus celecoxib and nsNSAIDs in the treatment of AS patients requiring daily NSAID treatment [
Transitions between different health states of Markov model due to events and lack of efficacy.
To | |||||||
From | Initial NSAID | Initial NSAID with PPI | Alternative nsNSAID | Alternative nsNSAID with PPI | Alternative nsNSAID with PPI & aspirin |
Anti-TNF | Discontinued Anti-TNF |
Initial NSAID | (i) No events | (i) Suspected PUB | (i) Edema, hypertension, hepatic, CHF, renal; all with switching treatment | Upper GI PUB | CV event | NA | NA |
Initial NSAID with PPI | NA | (i) Suspected PUB | NA | (i) Upper GI | CV event | NA | NA |
Alternative nsNSAID | NA | NA | (i) No events | (i) Suspected PUB | CV event | (i) Upper GI PUB | NA |
Alternative nsNSAID with PPI | NA | NA | NA | (i) Suspected PUB | CV event | (i) Upper GI PUB | NA |
Alternative nsNSAID with PPI & aspirin | NA | NA | NA | NA | Suspected PUB | (i) Upper GI PUB | NA |
Anti-TNF | NA | NA | NA | NA | NA | Other | Lack of efficacy |
Discontinued | NA | NA | NA | NA | NA | NA | All |
Tree structure reflecting events resulting in costs and potential changes in treatment (i.e., transitions between health states of the Markov model).
For each health state, utilities were assigned based on the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [
The model was developed with a cycle length of 1 year. The model followed individuals for a maximum of 30 cycles (30 years) as by this time the majority of individuals had reached the absorbing state (i.e., death).
The efficacy of etoricoxib, celecoxib, diclofenac, or naproxen in AS regarding BASFI, BASDAI, and discontinuation was obtained from a previously performed systematic review and Bayesian mixed treatment comparison (MTC) of randomized controlled trials using noninformative prior distributions [
Individual studies and results included for mixed treatment comparison of BASFI, BASDAI and discontinuation due to lack of efficacy.
Placebo | Celecoxib | Naproxen* | Etoricoxib | Diclofenac* | ||||||||
200 mg | 400 mg | 1000 mg | 90 mg | 150 mg | ||||||||
Mean | (SE) | Mean | (SE) | Mean | (SE) | Mean | (SE) | Mean | (SE) | Mean | (SE) | |
BASFI | ||||||||||||
Barkhuizen et al. [ | 2.00 | (3.00) | −9.00 | (0.50) | −11.00 | (1.00) | −16.00 | (2.00) | ||||
Van der Heijde et al. [ | −4.00 | (1.90) | −14.60 | (1.80) | −19.40 | (1.80) | ||||||
Dougados et al. [ | 1.30 | (2.03) | −11.90 | (2.46) | ||||||||
Sieper et al. [ | −8.00 | (1.62) | −9.00 | (1.23) | −9.00 | (1.45) | ||||||
BASDAI | ||||||||||||
Van der Heijde et al. [ | −6.40 | (1.90) | −23.6 | (1.80) | −28.60 | (1.80) | ||||||
Sieper et al. [ | −9.90 | (1.71) | −13.20 | (1.40) | −14.80 | (1.41) | ||||||
Discontinuation for lack of efficacy and (sample size) | ||||||||||||
Barkhuizen et al. [ | 59 | 156 | 25 | 137 | 23 | 161 | 17 | 157 | ||||
Van der Heijde et al. [ | 44 | 93 | 20 | 97 | 8 | 100 | ||||||
Dougados et al. [ | 31 | 76 | 18 | 80 |
*For mixed treatment comparison of BASDAI, the results of naproxen and diclofenac were considered as the group nsNSAID.
Parameters (and distributions) for cost-effectiveness evaluation.
Parameter | Value | Uncertainty range/95% credible interval | Assumed uncertainty distribution | Source |
---|---|---|---|---|
Change from baseline BASFI | ||||
Etoricoxib (90 mg) | −17.87 | −22.16; −13.64 | No distribution assumed; posterior distributions directly obtained from mixed treatment comparison of extracted data and simultaneously forwarded into Markov model. For MTC, noninformative prior distributions were used. |
Barkhuizen et al. [ |
Celecoxib (200 mg) | −10.12 | −12.34; −7.932 | ||
Celecoxib (400 mg) | −11.8 | −14.52; −9.10 | ||
Diclofenac | −11.51 | −15.68; −7.34 | ||
Naproxen | −14.82 | −17.69; −11.98 | ||
Change from baseline BASDAI | ||||
Etoricoxib (90 mg) | −28.53 | −32.06; −25.05 | Van der Heijde et al. [ | |
Celecoxib (200 mg) | −18.47 | −24.12; −12.9 | ||
Celecoxib (400 mg) | −21.77 | −26.95; −16.51 | ||
Diclofenac/naproxen | −23.46 | −26.96; −19.96 | ||
Probability of discontinuation | ||||
Etoricoxib (90 mg) | 0.063 | 0.027; 0.117 | ||
Celecoxib (200 mg) | 0.225 | 0.165; 0.292 | Barkhuizen et al. [ | |
Celecoxib (400 mg) | 0.177 | 0.113; 0.255 | Van der Heijde et al. [ | |
Diclofenac/naproxen | 0.149 | 0.105; 0.202 | Dougados et al. [ | |
BASFI without treatment | 45 | 40; 50 | Uniform (40, 50) | Based on baseline characteristics of trials included in MTC (see Table |
BASDAI without treatment | 45 | 40; 50 | Uniform (40, 50) | |
Disease progression measured using annual changes in BASFI | 0.5 | 0; 0.10 | Uniform (0, 0.10) | Kobelt et al. [ |
BASFI with anti-TNF | 23 | 20; 26 | Uniform (20, 26) |
Ara et al. [ |
BASDAI with anti-TNF | 19 | 18; 20 | Uniform (18, 20) | |
BASFI when stopped with anti-TNF | 55 | 50; 60 | Uniform (50, 60) | |
BASDAI when stopped with anti-TNF | 52 | 47; 57 | Uniform (47, 57) | |
Annual probability of discontinuation from anti-TNF | 0.10 | 0.05; 0.15 | Beta (13.2, 118.8) | Ara et al. [ |
PUBs | ||||
Etoricoxib | 0.0111 | 0.0074; 0.0159 | No distribution assumed; posterior distribution directly obtained from indirect comparison analysis of extracted data and simultaneously forwarded into Markov model. For indirect comparison of safety, noninformative prior distributions were used. |
Ramey et al. [ |
Celecoxib | 0.0134 | 0.0075; 0.0221 | ||
Diclofenac/naproxen | 0.0270 | 0.0216; 0.0334 | ||
Suspected PUBs | ||||
Etoricoxib | 0.0016 | 0.0000; 0.0061 | No distribution assumed; posterior distribution directly obtained from analysis of extracted data and simultaneously forwarded into Markov model. For indirect comparison of safety, noninformative prior distributions were used. |
Ramey et al. [ |
Celecoxib | 0.0016 | 0.0000; 0.0061 | ||
Diclofenac/naproxen | 0.0030 | 0.0000; 0.0115 | ||
Minor GI events |
MEDAL study [ | |||
Etoricoxib/celecoxib | 0.0463 | 0.0420; 0.0506 | ||
Diclofenac/naproxen | 0.0704 | 0.0650; 0.0759 | ||
PUB risk reduction with PPI | 0.40 | — | — | Moore et al. [ |
Dying from PUB | 0.036 | — | — |
Ramey et al. [ |
Hospitalization given PUB | 0.21 | 0.056; 0.358 | Uniform (0.056, 0.358) | Bloom et al. [ |
Surgery given hospitalization | 0.25 | 0.12; 0.39 | Uniform (0.12, 0.39) | Maetzel et al. [ |
Inpatient tx given suspected PUB | 0.25 | 0.18; 0.32 | Beta (36.5, 109.5) | Maetzel et al. [ |
Treatment given minor GI | 1 | — | — | Assumption |
Thrombotic CV event rate | No distribution assumed; posterior distribution directly obtained from indirect comparison analysis of extracted data and simultaneously forwarded into Markov model. For indirect comparison of safety, noninformative prior distributions were used. | |||
Etoricoxib | 0.0124 | 0.0111; 0.01381 |
Cannon et al. [ | |
Celecoxib | 0.0124 | 0.0111; 0.01381 | ||
Diclofenac | 0.0131 | 0.0117; 0.01454 | ||
Naproxen | 0.0077 | 0.0039; 0.01381 | ||
Death from thrombotic CV event |
Cannon et al. [ | |||
Etoricoxib/celecoxib | 0.13 | — | — | |
Diclofenac/naproxen | 0.128 | — | — | |
Edema |
MEDAL [ | |||
Etoricoxib/celecoxib | 0.0106 | 0.0086; 0.0127 | Beta (101.4, 9459.7) | |
Diclofenac/naproxen | 0.0070 | 0.0054; 0.0088 | Beta (64.9, 9165.4) | |
Hypertension | ||||
Etoricoxib/celecoxib | 0.0229 | 0.0200; 0.0260 | Beta (218.9, 9342.0) | |
Diclofenac/naproxen | 0.0153 | 0.0129; 0.0179 | Beta (141.2, 9088.8) | |
Coronary heart failure | ||||
Etoricoxib/celecoxib | 0.0044 | 0.0032; 0.0058 | Beta (42.1, 9518.9) | |
Diclofenac/naproxen | 0.0026 | 0.0017; 0.0037 | Beta (24.7, 9490.5) | |
Hepatic events | ||||
Etoricoxib/celecoxib | 0.0036 | 0.0025; 0.00489 | Beta (34.4, 9526.6) | |
Diclofenac/naproxen | 0.0218 | 0.0189; 0.0249 | Beta (201.2, 9028.8) | |
Renal events | ||||
Etoricoxib/Celecoxib | 0.0114 | 0.0094; 0.0136 | Beta (109.0, 9452.0) | |
Diclofenac/Naproxen | 0.0100 | 0.0081; 0.0120 | Beta (92.3, 9137.7) | |
Relation between EQ-5d and BASFI and BASDAI | Ara et al. [ | |||
Constant | 0.924 | 0.890; 0.957 | Normal (0.924, 0.0172) | |
BASFI | −0.004 | −0.0057; −0.0029 | Normal (−0.004, 0.00072) | |
BASDAI | −0.004 | −0.0056; −0.0024 | Normal (−0.004, 0.00082) | |
Surgery for PUB | 0.080 | 0.069; 0.092 | Beta distributions |
Moore et al. [ |
Inpatient treatment for PUB | 0.062 | 0.052; 0.072 | ||
Outpatient treatment for PUB | 0.051 | 0.042; 0.060 | ||
Inpatient investigation for suspected PUB | 0.062 | 0.052; 0.072 | ||
Outpatient investigation for suspected PUB | 0.025 | 0.021; 0.030 | ||
Minor GI symptoms requiring treatment | 0.015 | 0.012; 0.019 | ||
Minor GI symptoms not requiring treatment | 0.00004 | 0.00000; 0.00032 | ||
Thrombotic CV event | 0.294 | 0.256; 0.331 | Moore et al. [ | |
Edema | 0.020 | 0.016; 0.024 | Revicki [ | |
Hypertension | 0.001 | 0.000; 0.002 | Stason and Weinstein, [ | |
Hepatic | 0.055 | 0.040; 0.072 | Nichol et al. [ | |
CHF | 0.002 | 0.001; 0.002 | Wong et al, [ | |
Renal | 0.020 | 0.016; 0.024 | Revicki [ | |
Surgery for PUB | 22,904 | 18,900; 27,300 | ||
Inpatient treatment for PUB | 22,904 | 18,900; 27,300 | ||
Outpatient treatment for PUB | 2,231 | 2,038; 2,437 | Gamma distributions |
Resource use from Jansen et al. [ |
Inpatient investigation for suspected PUB | 22,295 | 18,240; 26,700 | ||
Outpatient investigation for suspected PUB | 1,297 | 1,157; 1,445 | ||
Minor GI symptoms requiring treatment | 568 | 507; 636 | ||
Thrombotic CV event | 95,555 | — | — | NoMA (September 2007); ISF 2007 [ |
CHF | 45,958 | — | — | NoMA (September 2007); ISF 2007 [ |
Etoricoxib (90 mg) | 4,654 | — | — | NoMA (September 2007) |
Celecoxib (200 mg) | 3,318 | — | — | |
Celecoxib (400 mg) | 6,636 | — | — | |
Diclofenac (150 mg) | 1,588 | — | — | |
Naproxen (1000 mg) | 1,380 | — | — | |
PPI (omeprazole) | 3,050 | — | — | |
Aspirin (75 mg) | 383 | — | — | |
Anti-TNF | 143,322 | — | — | NoMA (September 2007) |
For the model analysis, the expected change from baseline (CFB) estimates for BASFI and BASDAI by treatment were subtracted from background BASFI and BASDAI values which develop over time. Over time, an increase in BASFI of 0.5 (scale 0–100) per annum was assumed [
It was assumed that 10% withdraw from anti-TNF
An overview of all event-related parameters is presented in Table
The incidence of a thrombotic CV event with etoricoxib, diclofenac, and naproxen were obtained by performing an indirect comparison of the results from the MEDAL programme by Cannon et al. and the relative incidence rate of etoricoxib versus naproxen from a meta-analysis of thrombotic CV events in 12 phase II-IV clinical trials [
The adverse event rate for second-line nsNSAID therapy was assumed to be equal to the average of those obtained for diclofenac and naproxen, with the exception of the incidence of an upper GI event in a patient receiving nsNSAID plus PPI therapy, which was assumed to be reduced by 40% [
The case-fatality of a UGI PUB or LGI Bleed was 3.6% [
Utilities reflect the preference for a certain health state and are measured on 0-1 scale. A value of 1 reflects perfect health and 0 represents death. By summarizing the utility value over time, quality adjusted life years (QALYs) are created. Life years were transformed into QALYs using a relation between utility (EQ-5d) and BASFI and BASDAI as derived by Ara et al. [
Annual drug acquisition costs were calculated based on the most commonly prescribed drug within a drug class and obtained from the Norwegian Medicines Agency (NoMA September 2007). For anti-TNF treatment, annual costs of etanercept were used. For each type of GI event, numbers of units of health care resource use were assigned and respective unit costs applied to all healthcare resources to calculate the cost per event. The key cost items for GI events included costs of treatment (drugs and dispensing), GP consultations, investigations, inpatient days, and surgery. Costs of thrombotic CV events were weighted according to rates in the MEDAL study. All costs of adverse events were limited to the first year. Cost for the other adverse events (i.e., edema, hypertension, hepatic, and renal) were not taken into consideration. Drug costs related to adverse events were obtained from NoMA (September 2007); costs related to GP visits were obtained from the Norwegian Medical Association (July 2007), and inpatient costs related to events were obtained from the DRG price list [
Given the Markov state-transition model structure, the source data were combined and translated into the following outcomes: quality adjusted life years, drug acquisition costs, costs of adverse events, total costs, and net monetary benefit (NMB) calculated as QALYs multiplied with a willingness-to pay ratio (WTP) minus costs. WTP is the amount that decision makers are willing-to pay per additional QALY gained. Effects and costs were all discounted at 4% in the base-case scenario.
Since the model was fully probabilistic, outcomes were estimated with MCMC simulation using WinBUGS v 1.4. For each iteration of the model, new parameter values were sampled from the estimated (posterior) or defined distributions for efficacy, safety, and costs (see Table
In the base-case scenario, etoricoxib (90 mg) was compared with celecoxib (200 mg & 400 mg), diclofenac (150 mg), and naproxen (1000 mg). In alternative analyses, the following scenarios were evaluated: (1) celecoxib 200 mg was used instead of celecoxib 200 mg/400 mg, (2) only GI events, (3) only CV events, (4) no adverse events, (5) no discounting on costs and effects, (6) 8% discounting on costs and effects, (7) stable BASFI over time, and (8) assuming an age of 20 years, and (9) anti-TNF
In Table
Estimated effects and costs by treatment (base-case scenario).
Etoricoxib (90 mg) | Celecoxib (200 & 400 mg) | Diclofenac (150 mg) | Naproxen (1000 mg) | |||||||||
Estimate | 95% CrI | Estimate | 95% CrI | Estimate | 95% CrI | Estimate | 95% CrI | |||||
1 yrs | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
5 yrs | 4.59 | 4.59 | 4.60 | 4.59 | 4.59 | 4.60 | 4.59 | 4.59 | 4.59 | 4.59 | 4.59 | 4.60 |
30 yrs | 16.72 | 16.69 | 16.76 | 16.76 | 16.73 | 16.79 | 16.73 | 16.69 | 16.76 | 16.76 | 16.71 | 16.80 |
1 yrs | 0.74 | 0.66 | 0.80 | 0.67 | 0.59 | 0.75 | 0.69 | 0.61 | 0.76 | 0.70 | 0.62 | 0.77 |
5 yrs | 3.34 | 3.02 | 3.64 | 3.14 | 2.78 | 3.48 | 3.17 | 2.82 | 3.50 | 3.22 | 2.88 | 3.54 |
30 yrs | 11.16 | 9.85 | 12.42 | 10.66 | 9.24 | 12.04 | 10.71 | 9.30 | 12.08 | 10.80 | 9.41 | 12.15 |
98.90% | at 1 year | 0.00% | at 1 year | 0.13% | at 1 year | 0.98% | at 1 year | |||||
98.94% | at 5 years | 0.00% | at 5 years | 0.11% | at 5 years | 0.95% | at 5 years | |||||
99.96% | at 30 years | 0.00% | at 30 years | 0.00% | at 30 years | 0.04% | at 30 years | |||||
1 yrs | 4,654 | 4,654 | 4,654 | 4,977 | 4,977 | 4,977 | 1,588 | 1,588 | 1,588 | 1,380 | 1,380 | 1,380 |
5 yrs | 50,020 | 41,400 | 62,060 | 74,940 | 62,790 | 89,160 | 60,250 | 44,380 | 80,180 | 59,030 | 43,100 | 79,000 |
30 yrs | 628,200 | 463,300 | 823,600 | 740,500 | 544,400 | 971,100 | 710,400 | 517,500 | 937,800 | 708,900 | 516,200 | 936,000 |
1 yrs | 109 | 69 | 158 | 124 | 65 | 214 | 236 | 144 | 341 | 236 | 144 | 341 |
5 yrs | 554 | 360 | 784 | 648 | 391 | 977 | 939 | 576 | 1,356 | 943 | 579 | 1,361 |
30 yrs | 1,159 | 743 | 1,644 | 1,069 | 654 | 1,579 | 1,453 | 873 | 2,148 | 1,469 | 881 | 2,173 |
1 yrs | 1,148 | 1,027 | 1,278 | 1,148 | 1,027 | 1,278 | 1,208 | 1,082 | 1,345 | 714 | 360 | 1,271 |
5 yrs | 5,065 | 4,617 | 5,542 | 4,871 | 4,476 | 5,289 | 5,081 | 4,535 | 5,672 | 3,654 | 2,590 | 5,309 |
30 yrs | 10,060 | 8,452 | 11,650 | 7,696 | 6,712 | 8,756 | 8,293 | 6,852 | 9,920 | 6,541 | 4,888 | 8,833 |
1 yrs | 202 | 146 | 268 | 202 | 146 | 268 | 120 | 77 | 171 | 120 | 77 | 171 |
5 yrs | 814 | 612 | 1,048 | 723 | 555 | 918 | 502 | 323 | 718 | 504 | 324 | 720 |
30 yrs | 1,507 | 1,098 | 1,991 | 1,048 | 795 | 1,342 | 820 | 513 | 1,201 | 828 | 517 | 1,214 |
1 yrs | 6,115 | 5,974 | 6,267 | 6,452 | 6,300 | 6,618 | 3,152 | 2,981 | 3,332 | 2,449 | 2,073 | 3,015 |
5 yrs | 56,450 | 47,920 | 68,450 | 81,190 | 69,120 | 95,230 | 66,780 | 51,010 | 86,440 | 64,130 | 48,120 | 84,220 |
30 yrs | 640,900 | 476,900 | 835,600 | 750,300 | 554,500 | 980,800 | 721,000 | 528,800 | 947,700 | 717,800 | 526,000 | 944,700 |
0.00% | at 1 year | 0.00% | at 1 year | 1.15% | at 1 year | 98.85% | at 1 year | |||||
85.26% | at 5 years | 0.00% | at 5 years | 0.18% | at 5 years | 14.57% | at 5 years | |||||
98.92% | at 30 years | 0.01% | at 30 years | 0.03% | at 30 years | 1.04% | at 30 years |
1All results are discounted, 4.0% for effects and costs.
2Probability that a certain intervention provides best outcomes (i.e., greatest QALYs, lowest costs).
Drug costs are expected to be the highest with celecoxib (200 & 400 mg) followed by etoricoxib (90 mg). The nsNSAIDs result in the lowest drug costs. After 5 years, however, the lowest drug costs can be expected for the patients for whom treatment was initiated with etoricoxib due to the higher probability of staying on initial therapy and not switching to the far more expensive anti-TNF
Relative to a patient starting with nsNSAIDs, the costs due to GI events were lower for a patient starting with etoricoxib or celecoxib as a result of a reduced risk of treatment-requiring GI events. After 30 years, the GI-related costs with etoricoxib were higher than with celecoxib because this latter group of patients switched quicker to anti-TNF
In Table
Cost-effectiveness of etoricoxib relative to other interventions (base-case scenario).
Incremental costs in NOK | Incremental QALYs | Incremental cost-effectiveness ratio | |||||||
Estimate | 95% CrI | Estimate | 95% CrI | Estimate | 95% CrI | ||||
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | −337 | −411 | −280 | 0.06 | 0.03 | 0.10 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus diclofenac | 2,964 | 2,753 | 3,173 | 0.05 | 0.02 | 0.09 | 59,221 | 33,180 | 184,500 |
Etoricoxib (90 mg) versus naproxen | 3,666 | 3,109 | 4,046 | 0.03 | 0.01 | 0.07 | 107,256 | 51,320 | 494,300 |
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | −24,730 | −37,730 | −11,720 | 0.20 | 0.08 | 0.33 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus diclofenac | −10,320 | −26,070 | 2,840 | 0.17 | 0.05 | 0.30 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus naproxen | −7,682 | −23,540 | 5,729 | 0.12 | 0.02 | 0.23 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | −109,400 | −198,700 | −38,640 | 0.51 | 0.25 | 0.84 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus diclofenac | −80,060 | −164,800 | −13,280 | 0.45 | 0.20 | 0.76 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus naproxen | −76,850 | −162,100 | −9,622 | 0.36 | 0.13 | 0.66 | Dominant | Dominant | Dominant |
Cost-effectiveness acceptability curves reflecting the probability of cost-effectiveness for etoricoxib, celecoxib (200 & 400 mg), diclofenac, and naproxen at a followup of 1 year, 5 years, and 30 years (base-case scenario).
Proportion of explained uncertainty in model outcomes (incremental QALYs, costs, and net-monetary benefit at WTP of 400,000 NOK) by the most relevant variables for the comparison of etoricoxib (90 mg) versus celecoxib, diclofenac, and naproxen (base-case scenario).
When celecoxib 200 mg was used as a comparator instead of celecoxib 200 mg & 400 mg combined, etoricoxib was no longer economically dominant at 1 year. Etoricoxib is 1,322 NOK more expensive. Given the QALY gain of 0.07, this translates into a cost per QALY of 17,882 NOK, a cost-effective result.
Scenarios where (1) only GI events were included as adverse events, (2) only CV events were included as adverse events, (3) no adverse events were included, (4) no discounting was applied, (5) 8% discounting was applied, (6) BASFI was assumed to be stable over time, and (7) assuming an average age of 20 years provided comparable cost-effectiveness results as the base-case analysis. Only for the scenario where anti-TNF
Cost-effectiveness of etoricoxib relative to other interventions when anti-TNF
Incremental costs in NOK | Incremental QALYs | ICER | |||||||
Estimate | 95% CrI | Estimate | 95% CrI | Estimate | 95% CrI | ||||
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | −337 | −410 | −280 | 0.06 | 0.03 | 0.10 | Dominant | Dominant | Dominant |
Etoricoxib (90 mg) versus diclofenac | 2,965 | 2,756 | 3,173 | 0.05 | 0.02 | 0.09 | 59,288 | 33,190 | 188,200 |
Etoricoxib (90 mg) versus naproxen | 3,663 | 3,099 | 4,043 | 0.03 | 0.01 | 0.07 | 107,074 | 50,970 | 488,500 |
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | 2,194 | 426 | 3,745 | 0.20 | 0.08 | 0.33 | 10,926 | 2083 | 30820 |
Etoricoxib (90 mg) versus diclofenac | 10,560 | 9,058 | 11,880 | 0.17 | 0.05 | 0.30 | 62,411 | 34650 | 198400 |
Etoricoxib (90 mg) versus naproxen | 12,370 | 10,330 | 14,000 | 0.12 | 0.02 | 0.23 | 103,083 | 49220 | 465100 |
Etoricoxib (90 mg) versus celecoxib (200 & 400 mg) | 15,740 | 5,398 | 25,490 | 0.51 | 0.25 | 0.84 | 31,009 | 14330 | 59810 |
Etoricoxib (90 mg) versus diclofenac | 23,910 | 14,520 | 32,990 | 0.45 | 0.20 | 0.76 | 53,181 | 34020 | 103800 |
Etoricoxib (90 mg) versus naproxen | 25,660 | 16,150 | 34,810 | 0.36 | 0.13 | 0.66 | 70,825 | 42830 | 170900 |
The economic evaluation demonstrated that etoricoxib (90 mg) is an economically superior treatment of AS to celecoxib (200 & 400 mg), diclofenac (150 mg), and naproxen (1000 mg) for both QALY gains and cost savings for a time horizon longer than 5 years. For a 1-year time horizon, etoricoxib is associated with greater costs than diclofenac (150 mg) and naproxen (1000 mg), but can still be considered cost effective.
In addition to drug acquisition costs for the NSAIDs, also costs for anti-TNF
For the current economic evaluation, a comprehensive decision modeling approach was used. With this approach, an indirect comparison of efficacy and safety estimates were integrated with cost-effectiveness analysis in a single framework [
The etoricoxib GI safety data as used in the analysis were obtained from clinical trials in OA, RA, AS, and chronic low back pain patients [
In the model, the risk for a second CV event was set to be the same as before the CV event, assuming that the increased CV risk due to the history of a CV event was counterbalanced by adding aspirin to the NSAID. However, the history of a CV event might have a bigger impact than the protective effect by aspirin, which would imply an underestimation of the risk of CV events in the model, and, therefore, an underestimation of the costs due to CV events. The effect on the difference in costs, however, would be limited because the underestimation applies to both treatment initiated with etoricoxib and nsNSAIDs.
Costs associated with severity of AS (i.e., GP visits, specialist visits, paramedical visits, hospitalization, technical examinations, adaptations and aids) were not included in the analysis. For the UK, Botteman et al. showed that each incremental change in one unit of BASDAI (0–100 scale) was estimated to be associated with a direct medical cost increase according to Cost =
This evaluation was performed for the Norwegian local situation. In general, it is difficult to “transfer” cost-effectiveness estimates obtained for one country to another, due to differences in treatment practices, resource use, and unit cost data, among other. Although the cost-effectiveness findings in this study were primarily driven by differences in efficacy of the compared interventions, the cost-effectiveness of the different NSAIDs for the management of ankylosing spondylitis in other countries needs to be confirmed with country-specific analysis.
In conclusion, given the underlying assumptions and current evidence available, this economic evaluation demonstrated that etoricoxib is a cost-saving and QALY gaining therapy for AS in Norway from a health care perspective.
This study was funded by Merck & Co., Inc.
J. P. Jansen is an employee of Mapi Values. Mapi Values received consultancy fees from Merck & Co. Inc. related to this paper. S. Taylor is an employee of Merck & Co. Inc.