Background and Aims: The well-recognized gastrointestinal toxicity of NSAIDs ranges from mild symptoms to severe complications requiring medical attention and leading to work loss. The present study evaluates the economic burden derived from health care resource utilization and work loss caused by NSAID-induced gastrointestinal toxicity in the Swiss population. The costs induced by conventional and COX2-selective NSAIDs were calculated separately, and the results were then extrapolated for the United States. Methods: A computer-generated random sampling of the Swiss population (n = 6,118) was administered a questionnaire by phone. Questions investigated NSAID intake, occurrence of adverse effects, consumption of gastroprotective drugs, health care resource utilization and work loss. Country-specific direct and indirect costs associated with NSAID-induced gastrointestinal toxicity were calculated according to current reimbursement costs in Switzerland and the United States. Medication expenses were used to compute separate iatrogenic cost factors for conventional and COX2-selective NSAIDs. The ability of demographic variables and symptoms to predict resource utilization was analyzed by univariate and multivariate analyses. Results: From among the 6,085 responders (99.5% response rate), 294 subjects had gastrointestinal adverse effects associated with NSAID intake. The annual amount spent on NSAID-related adverse effects was CHF 432.2 million for Switzerland and USD 7,425.7 million for the United States. This amount corresponded to CHF 581 and USD 272 per NSAID user, and was primarily due to costs derived from work loss. For Switzerland, 91.1% of total costs were associated with the use of conventional NSAIDs and could be saved by using COX2-NSAIDs instead. While additional 13% of the medication purchase costs are spent for gastrointestinal adverse effects among COX2-selective NSAID users, additional 315% are spent for the same reason among conventional NSAID users. Thus, given similar efficacy and purchase costs in the two drug groups, COX2-selective NSAIDs are 25.1 times more cost-effective than conventional NSAIDs. Language region, place of residence, nationality, marital status, epigastric pain, diarrhea, hematemesis and melena predicted resource utilization. Conclusions: Costs arising from NSAID-induced gastrointestinal toxicity are considerable and primarily associated with conventional NSAIDs. COX2-selective NSAIDs could decrease this economic burden.

1.
Gibson T: Nonsteroidal anti-inflammatory drugs – another look. Br J Rheumatol 1989;27:87–90.
2.
Steward RB, Hale WE, Marks RG: Analgesic drug use in an ambulatory elderly population. Drug Intell Clin Pharm 1982;16:833–836.
3.
Chrischilles EA, Lemke JH, Wallace RB, Drube GA: Prevalence and characteristics of multiple analgesic drug use in an elderly study group. J Am Geriatr Soc 1990;38:979–984.
4.
Lichtenstein DR, Syngal S, Wolfe MM: Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract: The double edged sword. Arthritis Rheum 1995;38:5–18.
[PubMed]
5.
Allison MC, Howatson AG, Torrance CJ, Lee FD, Russel RI: Gastrointestinal damage associated with the use of nonsteroidal anti-inflammatory drugs. N Engl J Med 1992;327:749–754.
[PubMed]
6.
Singh G, Rosen Ramey D: NSAID induced gastrointestinal complications: The ARAMIS perspective – 1997. Arthritis, Rheumatism, and Aging Medical Information System. J Rheumatol Suppl 1998;51:8–16.
[PubMed]
7.
Singh G, Triadafilopoudus G: Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999;26(suppl 56):18–24.
8.
Puspok A, Kiener HP, Oberhuber G: Clinical, endoscopic, and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon. Dis Colon Rectum 2000;43:685–691.
9.
Lanas A, Bajador E, Serrano P, Fuentes J, Carreno S, Guardia J, Sanz M, Montoro M, Sainz R: Nitrovasodilatators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834–839.
[PubMed]
10.
Wolfe MM, Lichtenstein DR, Singh G: Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 1999;340:1888–1899.
[PubMed]
11.
Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, Geis GS: Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995;123:241–249.
[PubMed]
12.
Fries JF, Williams CA, Bloch DA, Michel BA: Nonsteroidal anti-inflammatory drug-associated gastropathy: Incidence and risk factors models. Am J Med 1991;91:213–222.
[PubMed]
13.
Savage RL, Moller PW, Ballantyne CL, Wells JE: Variation in the risk of peptic ulcer complications with nonsteroidal anti-inflammatory drug therapy. Arthritis Rheum 1993;36:84–90.
[PubMed]
14.
Langman MJ, Weil J, Wainwright P, Lawson DH, Rawlins MD, Logan RF, Murphy M, Vessey MP, Colin-Jones DG: Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994;343:1075–1078.
[PubMed]
15.
Blot WJ, McLaughlin JK: Over the counter non-steroidal anti-inflammatory drugs and of gastrointestinal bleeding. J Epidemiol Biostat 2000;5:137–142.
16.
Seibert K, Masferrer JL, Fu YJ, Honda A, Raz A, Needleman P: The biochemical and pharmacological manipulation of cellular cyclooxygenase (COX) activity. Adv Prostaglandin Thromboxane Leukot Res 1991;21A:45–51.
17.
Needleman P, Isakson PC: The discovery and function of COX-2. J Rheumatol 1997;24 (suppl 49):6–8.
18.
Simon LS: Role and regulation of cyclooxygenase-2 during inflammation. Am J Med 1999;106:37S–42S.
19.
Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998;104:413–421.
[PubMed]
20.
Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, Isakson PC, Geis GS: Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: Efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998;41:1591–1602.
[PubMed]
21.
Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247–1255.
[PubMed]
22.
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343:1520–1528.
[PubMed]
23.
Bensen WG, Zhao SZ, Burke TA, Zabinski RA, Makuch RW, Maurath CJ, Agrawal NM, Geis GS: Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo. J Rheumatol 2000;27:1876–1883.
[PubMed]
24.
Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, Isakson PC, Verburg KM, Yu SS, Zhao WW, Geis GS: Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: A randomized controlled trial. JAMA 2000;282:1921–1928.
25.
Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, Stern S, Quan H, Bolognese J: A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology 1999;117:776–783.
[PubMed]
26.
Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Verburg KM, Isakson PC, Hubbard RC, Geis GS: Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: Randomised double-blind comparison. Lancet 1999;354:2106–2111.
[PubMed]
27.
Buttgereit F, Burmester GR, Simon LS: Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors. Am J Med 2001;110 (suppl 3A):13S–19S.
28.
Dougados M, Behier JM, Jolchine I, Calin A, van der Heijde D, Olivieri I, Zeidler H, Herman H: Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: A six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Arthritis Rheum 2001;44:180–185.
29.
Taylor B, van de Wal B: Safety of celecoxib vs. other nonsteroidal anti-inflammatory drugs. JAMA 2000;284:3123–3124.
30.
Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ: Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999;282:1929–1933.
[PubMed]
31.
Jackson LM, Hawkey CJ: COX-2 selective nonsteroidal anti-inflammatory drugs: Do they really offer any advantages? Drugs 2000;59:1207–1216.
[PubMed]
32.
Hawkey CJ, Jackson L, Harper SE, Simon TJ, Mortensen E, Lines CR: Review article: The gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans. Aliment Pharmacol Ther 2001;15:1–9.
[PubMed]
33.
Goldstein JL: Significant upper gastrointestinal events associated with conventional NSAID versus celecoxib. J Rheumatol Suppl 2000;60:25–28.
34.
Bloom BS: Direct medical costs of disease and gastrointestinal side effects during treatment of arthritis. Am J Med 1988;84:20–24.
35.
Bloom BS: Cost of treating arthritis and NSAID-related gastrointestinal side-effects. Aliment Pharmacol Ther 1988;2(suppl 1):131–138.
36.
Bloom BS: Risk and cost of gastrointestinal side effects associated with nonsteroidal anti-inflammatory drugs. Arch Intern Med 1989;149:1019–1022.
[PubMed]
37.
Blomqvist P, Feltelius N, Ekbom A, Klareskog L: Rheumatoid arthritis in Sweden: Drug prescriptions, costs, and adverse drug reactions. J Rheumatol 2000;27:1171–1177.
[PubMed]
38.
Rahme E, Joseph L, Kong SX, Watson DJ, LeLorier J: Gastrointestinal health care resource use and costs associated with nonsteroidal antiinflammatory drugs versus acetaminophen: Retrospective cohort study of an elderly population. Arthritis Rheum 2000;43:917–924.
[PubMed]
39.
Hawkey CJ, Cullen DJ, Greenwood DC, Wilson JV, Logan RF: Prescribing of nonsteroidal anti-inflammatory drugs in general practice: Determinants and consequences. Aliment Pharmacol Ther 1997;11:293–298.
40.
Walan A, Wahlqvist P: Pharmacoeconomic aspects of non-steroidal anti-inflammatory drug gastropathy. Ital J Gastroenterol Hepatol 1999;31(suppl 1):S79–88.
41.
Chevat C, Pena BM, Al MJ, Rutten FF: Healthcare resource utilisation and costs of treating NSAID-associated gastrointestinal toxicity: A multinational perspective. Pharmacoeconomics 2001;19(suppl 1):17–32.
42.
Hunsche E, Chancellor JV, Bruce N: The burden of arthritis and nonsteroidal anti-inflammatory treatment: A European literature review. Pharmacoeconomics 2001;19(suppl 1):1–15.
43.
Kolodny AL, Klipper A: Final report on the cost of treating arthritic disease: Comparison between salicylates and nonsalicylate nonsteroidal anti-inflammatory drugs. Semin Arthritis Rheum 1985;14(3 suppl 1):20–24.
44.
McGoldrick MD, Bailie GR: Nonnarcotic analgesics: Prevalence and estimated economic impact of toxicities. Ann Pharmacother 1997;31:221–227.
45.
De Pouvourville G: The iatrogenic cost of non-steroidal anti-inflammatory drug therapy. Br J Rheumatol 1995;34 (suppl 1):19–24.
46.
De Pouvourville G: The economic consequences of NSAID-induced gastropathy: The French context. Scand J Rheumatol Suppl 1992;96:49–53.
47.
Knill-Jones RP: The economic consequences of NSAID-induced gastropathy in the United Kingdom and commentary on the article by G de Pouvourville. Scand J Rheumatol Suppl 1992;96:59–62.
[PubMed]
48.
Johnson RE, Hornbrook MC, Hooker RS, Woodson GT, Shneidman R: Analysis of the costs of NSAID-associated gastropathy: Experience in a US health maintenance organisation. Pharmacoeconomics 1997;12:76–88.
[PubMed]
49.
Moore RA, Phillips CJ: Cost of NSAID adverse effects to the UK National Health Service. J Med Economics 1999;2:45.
50.
Moore N, Verschuren X, Montout C, Callens J, Kong SX, Begaud B: Excess costs related to non-steroidal anti-inflammatory drug utilization in general practice. Therapie 2000;55:133–136.
51.
Die Spitäler der Schweiz. H+ Spitalstatistiken. Panoptikum: Medizinische Statistik 1996, administrative Statistik 1996. 27. Band. Aarau, H+ Verlag, 1997.
52.
Arzneimittel Brevier 2001. Ed. J Morant. Basel, Documed AG, 2000.
53.
Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, Swannell AJ, Hawkey CJ: A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med 1998;338:719–726.
[PubMed]
54.
Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A, Swannell AJ, Yeomans ND: Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) Study Group. N Engl J Med 1998;338:727–734.
[PubMed]
55.
Kirschner CG, Davis SJ, Evans D, Hayden D, Jackson JA, Jacobson CA, et al: Physicians’ Current Procedural Terminology CPT. Chicago, American Medical Association, 1999.
56.
Seare S, Speirs L, Bernard SP, Turner K, Neeshan C: DRG Guide 1998. Salt Lake City, Medicode, 1997.
57.
Medicare Services, Provider Information. URL: http:/www.oknmmedicare.com/provider/disclosure/discsearch.asp accessed March 30, 2001.
58.
Personal communication from the Revenue Section, Financial Management Service of the Veterans Affairs Medical Center, Albuquerque, NM, April 11, 2001.
59.
US Department of Labor, Bureau of Labor Statistics. URL: http://stats.bls.gov/pdf/cpsaat37.pdf accessed April 8, 2001.
60.
PDR.net, Medical Economics Company Inc., The Red Boook 2001 online. URL: http://physician.pdr.net/physician/redbook/redbooklev2.htm accessed April 1, 2001.
61.
US Census Bureau, Population Division. URL: http://www.census.gov/population/estimates/nation/intfile2-1.txt accessed April 2, 2001.
62.
Swiss Federal Office of Statistics, section Health. URL:http://www.statistik.admin.ch/stat_ch/ber14/gewe/dtfr14b.htm accessed May 12, 2001.
63.
US Census Bureau. URL: http://www.census.gov/statab/freq/00s0152.xls accessed May 12, 2001.
64.
Swiss Federal Office of Statistics, section National Economy. URL: http://www.statistik. admin.ch/stat_ch/ber04/du0401.htm accessed May 12, 2001.
65.
US Department of Commerce. URL: http://www.bea.doc.gov/bea/newsrel/gdp101a.htm accessed May 12, 2001.
66.
Hennekens CH, Buring JE: In Mayrent SL (ed): Epidemiology in Medicine, ed 1. Boston, Little, Brown, 1987, pp 87–95.
67.
SPSS Version 10.0 US English for Windows. Chicago, SPSS, 2000.
68.
Rosner B: Fundamentals of Biostatistics, ed 4. Belmont, Duxbury Press, 1995.
69.
Kleinbaum DG: In Dietz K, Gail M, Krickeberg K, Singer B (eds): Logistic Regression: A Self-Learning Text. New York, Spinger, 1998.
70.
Gabriel SE, Fehring RA: Trends in the utilization of non-steroidal anti-inflammatory drugs in the United States, 1986–1990. J Clin Epidemiol 1992;45:1041–1044.
[PubMed]
71.
Fries JF: NSAID gastropathy: Epidemiology. J Muskuloskel Med 1991;8:21–28.
72.
Day R, Morrison B, Luza A, Castaneda O, Strusberg A, Nahir M, Helgetveit KB, Kress B, Daniels B, Bolognese J, Krupa D, Seidenberg B, Ehrich E: A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/Ibuprofen Comparator Study Group. Arch Intern Med 2000;160:1781–1787.
[PubMed]
73.
Cannon GW, Caldwell JR, Holt P, McLean B, Seidenberg B, Bolognese J, Ehrich E, Mukhopadhyay S, Daniels B: Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: Results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Rofecoxib Phase III Protocol 035 Study Group. Arthritis Rheum 2000;43:978–987.
[PubMed]
74.
Ehrich EW, Schnitzer TJ, McIlwain H, Levi R, Wolfe F, Weisman M, Zeng Q, Morrison B, Bolognese J, Seidenberg B, Gertz BJ: Effect of specific COX-2 inhibition in osteoarthritis of the knee: A 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group. J Rheumatol 1999;26:2438–2447.
[PubMed]
75.
Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM, Hubbard RC, Isakson PC, Verburg KM, Geis GS: Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: A randomized controlled trial. Mayo Clin Proc 1999,74:1095–1105.
76.
Fries JF: NSAID gastropathy: The second most deadly rheumatic disease? Epidemiology and risk appraisal. J Rheumatol Suppl 1991;28:6–10.
[PubMed]
77.
Singh G: Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med 1998;105:31S–38S.
78.
Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA: Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology 1989;96(suppl):647–655.
79.
Drummond MF, O’Brien B, Stoddart GL, Torrance GW: Methods for the Economic Evaluation of Health Care Programmes, ed 2. New York, Oxford University Press, 1997.
You do not currently have access to this content.