Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

Soo-Jin Chung; Hye-Jin Park; Min-Chan Park

doi:10.4078/jrd.2017.24.1.27

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Chung, Park, and Park: Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

Original Article

J Rheum Dis 2017;24(1):27-34.

Published online: 31 October 2017

DOI: https://doi.org/10.4078/jrd.2017.24.1.27

Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

Soo-Jin Chung¹, Hye-Jin Park², Min-Chan Park¹

¹Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

²School of Pharmacy, Sungkyunkwan University, Suwon, Korea

Corresponding to: Min-Chan Park, Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea. E-mail: mcpark@yuhs.ac

Received 24 March 2016 Revised 6 January 2017 Accepted 12 January 2017

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, nonselective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA).

Methods

A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea.

Results

The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior.

Conclusion

COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea.

Keywords: Cost-effectiveness, Cox-2 selective inhibitor, Gastrointestinal toxicity, Non-steroidal anti-inflammatory drugs, Rheumatoid arthritis

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Figure 1.

Part of a decision tree for cost-effectiveness of rheumatoid arthritis treatment. Three strategies are modeled by non-steroidal anti-inflammatory drug (naproxen or meloxicam), celecoxib, and NSAID with PPI. NSAID: non-steroidal antiinflammatory drug, PPI: proton-pump inhibitor, GI: gastrointestinal, UGI: upper gastrointestinal, LGI: lower gastrointestinal, EGD: esophagogastroduodenoscopy, MED: medication, CT: computed tomography.

Table 1.

Health transition probability

Health transition	Probability (%)	Source
Improve RA
NSAIDs	36	CLASS study^∗
Celecoxib	38	CLASS study^∗
NSAIDs+PPI	36	CLASS study^∗
Death	0.00137	Korea National
		Statistical Office,
		Statistical Database
Clinical UGI events
NSAIDs	0.362	CLASS study^∗
Celecoxib	0.308	CLASS study^∗
NSAID+PPI	0.308	Author's best estimate^†
Uncomplicated ulcer
NSAIDs	0.169	CLASS study^∗
Celecoxib	0.110	CLASS study^∗
NSAID+PPI	0.110	Author's best estimate^†
UGI Bleeding
NSAIDs	0.116	CLASS study^∗
Celecoxib	0.058	CLASS study^∗
NSAID+PPI	0.058	Author's best estimate^†
UGI Perforation
NSAIDs	0.000	CLASS study^∗
Celecoxib	0.000	CLASS study^∗
NSAID+PPI	0.000	Author's best estimate^†
Clinical LGI events
NSAIDs	4.757	CLASS study^∗
Celecoxib	3.387	CLASS study^∗
NSAID+PPI	4.757	Author's best estimate^‡
LGI Bleeding
NSAIDs	0.379	CLASS studya^∗
Celecoxib	0.197	CLASS studya^∗
NSAID+PPI	0.379	Author's best estimate^‡
LGI Perforation
NSAIDs	0.012	CLASS study^∗
Celecoxib	0.000	CLASS study^∗
NSAID+PPI	0.012	Author's best estimate^‡

RA: rheumatoid arthritis, NSAIDs: non-steroidal antiinflammatory drugs, PPI: proton pump inhibitor, UGI: upper gastrointestinal, LGI: lower gastrointestinal, CLASS: Celecoxib Long-Term Arthritis Safety Study, GI: gastrointestinal.

^* CLASS clinical study.

^† GI toxicitiy of NSAID with PPI might be equal with that if celecoxib treatment.

^‡ PPI could not prevent lower GI complications.

Table 2.

Utility of health status

Health status	QOL	Source
RA	0.688	[26]
Complete recovery from RA	1
Death	0
Clinical upper GI events	0.504	[26]
Uncomplicated upper GI ulcer	0.38	[26]
Upper GI bleeding	0.312	[26]
Upper GI perforation	0	[26]
Clinical lower GI events	0.504	Author's best estimate^∗
Lower GI bleeding	0.312	Author's best estimate^∗
Lower GI perforation	0	Author's best estimate^∗

QOL: quality of life, RA: rheumatoid arthritis, GI: gastrointestinal.

^* The QOL scores of lower GI complications were estimated to be equal to those of upper GI complications.

Table 3.

Estimated costs of treatment for gastrointestinal complications

Data	Cost (USD)	Source
Drug cost^∗
Celecoxib 200 mg bid	44	Health Insurance Review and Assessment Services
Naproxen 500 mg bid	9	Health Insurance Review and Assessment Services
Meloxicam 7.5 mg bid	19	Health Insurance Review and Assessment Services
Omeprazole 20 mg qd	23	Health Insurance Review and Assessment Services
Cimetidine 800 mg qd	4	Health Insurance Review and Assessment Services
Monitoring cost	10	National Health Statistical Yearbook^‡
Distribution cost^†	11	National Health Statistical Yearbook^‡
GI complications
Clinical UGI event	137	Hospital data^§
Uncomplicated ulcer	137	Hospital data^§
UGI bleeding	1,329	Hospital data^§
UGI perforation	6,134	Hospital data^§
Clinical LGI event	1,400	Hospital data^§
LGI bleeding	3,163	Hospital data^§
LGI perforation	14,010	Hospital data^§

USD: United States dollar, bid: twice per day, qd: once per day, GI: gastrointestinal, UGI: upper gastrointestinal, LGI: lower gastrointestinal.

^* Drug costs were calculated over a 4 week period.

^† Distribution costs were calculated over a 12 week period.

^‡ National Health Insurance Corporation, Health Insurance Review & Assessment Services; 2011∼2012 National Health Statistical Yearbook.

^§ Obtained from patients who had been treated in a tertiary referral center, Seoul, South Korea.

Table 4.

Cost effectiveness of three treatment strategies

Strategy	Total cost (KRW)	Effectiveness (QALY)	ICER
Celecoxib	3,052,800	2.87446	Dominant^*
NSAID	3,170,800	2.85320	Dominated^†
NSAID+PPI	3,325,900	2.85533	Dominated^†

KRW: Korean won, QALY: quality-adjusted life year, ICER: incremental cost effectiveness ratio, NSAID: non-steroidal anti-inflammatory drug, PPI: proton-pump inhibitor.

^* The intervention costs less and is at least as effective as the comparator.

^† The intervention costs more and is no more effective than the comparator.

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