Management of NSAID-induced gastropathy: an economic decision analysis

doi:10.1016/S0149-2918(97)80021-5

Clinical Therapeutics

Volume 19, Issue 6, November–December 1997, Pages 1496-1509

https://doi.org/10.1016/S0149-2918(97)80021-5 Get rights and content

Abstract

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a 2% to 4% annual incidence of serious gastrointestinal complications. These adverse clinical outcomes, and the strategies used to prevent their occurrence, translate into a significant economic burden. A decision-analysis model was constructed to contrast the 6-month costs associated with various approaches to preventing and managing NSAID-induced gastropathy and to evaluate the economic impact of two treatment regimens using fixed-dose formulations of diclofenac/misoprostol. After incorporating expected medical outcomes and predicted practice patterns, 6-month per-patient costs were derived from the model for each of five treatment regimens: (1) NSAID alone; (2) NSAID with a histamine₂-receptor antagonist; (3) NSAID with coprescribed misoprostol; (4) diclofenac/misoprostol 50 mg/200 μg TID/BID; and (5) diclofenac/misoprostol 75 mg/200 μg BID. The combined diclofenac/misoprostol regimens demonstrated an 18.6% per-patient cost advantage compared with the combined NSAID regimens. Based on a 6-month period, this cost savings translated into a $214.00 per-patient overall cost savings ($1153.00 per patient for NSAID regimens versus $939.00 for diclofenac/misoprostol regimens). The magnitude of this difference was verified by Monte Carlo simulation. Despite the considerable cost difference, sensitivity analyses revealed that our model was robust and that no single variation substantially influenced the results. Given the lack of long-term prospective, comparative clinical-outcomes studies in this area, this decision analysis provides guidance to clinicians in developing a rational and cost-effective approach to the treatment of patients requiring chronic NSAID therapy.

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Cited by (21)

Cost-effectiveness of Low-dose Submicron Diclofenac Compared With Generic Diclofenac
2016, Clinical Therapeutics
Citation Excerpt :
In our study, we used the diclofenac dose–toxicity relationship estimated by Odom et al19 as key input for a decision-analytic model, which we developed to estimate the economic and health benefits of submicron diclofenac in reducing AEs, assuming pain relief similar to that with generic diclofenac, from a US payer’s perspective. Prior to formulating the model, we reviewed economic models presented in health technology assessment reports by the UK National Institute for Health and Care Excellence21–23 as well as published economic models that analyzed the cost-effectiveness of various NSAID-prescribing strategies that might reduce the occurrence of NSAID-induced AEs.24–32 These decision-analytic models included GI-related AEs such as GI discomfort or dyspepsia; symptomatic ulcer; serious peptic ulcer complication that leads to hospital admission; serious GI event or complication that requires a hospitalization; serious GI event or complication that leads to death, obstruction, bleeding, and/or ulcer; and peptic ulcer bleeding.
NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose–toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose–related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States.
Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses.
The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18.0%), cardiovascular events (by 6.9%), and acute renal failure (by 18.8%), leading to a 9.8% reduction in costs of treating AEs. Submicron diclofenac was predicted to be cost-saving, with results relatively insensitive to parameter uncertainty.
Submicron diclofenac has the potential to provide clinical and economic value to patients using NSAIDs in the United States. Further investigation regarding the potential effects of submicron diclofenac on the risks for additional NSAID dose-related toxicities should be explored.
Gastrointestinal toxicity associated with nonsteroidal anti-inflammatory drugs: Epidemiologic and economic issues
2001, Gastroenterology Clinics of North America
Citation Excerpt :
Despite the availability of some newer NSAIDs as well as gastroprotective drugs, the iatrogenic cost factor may not have decreased over 15 years. Numerous economic analyses of the cost-effectiveness of misoprostol to prevent the serious gastrointestinal complications of NSAIDs have been performed.7,15,18,20,27,35,51,54,67 Gabriel and Wagner28 summarized the challenges in interpreting this literature: There was significant variation across virtually all methodologic parameters, making it problematic to compare the results of different studies.
Economic evaluation of rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs for the treatment of osteoarthritis
2001, Clinical Therapeutics
Background: Results of phase III clinical trials of rofecoxib, a selective inhibitor of cyclooxygenase 2, have shown that osteoarthritis patients treated with rofecoxib had significantly fewer clinically significant gastrointestinal (GI) adverse events than those who received nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).
Objective: This paper explores the potential economic implications of the use of rofecoxib versus nonselective NSAIDs for the treatment of osteoarthritis via a decision analytic model based on rofecoxib clinical data and the published literature.
Methods: Base-case 1-year analyses were done with data on GI adverse events, specifically perforations, ulcers, and bleeds (PUBs), obtained from a prespecified pooled analysis of the rofecoxib clinical trials. Analyses were also performed using pooled results of two 12-week endoscopic surveillance trials, with adjustments for silent ulcers of 40% and 85%.
Results: Under base-case conditions, the expected cost savings in GI problems and comedications averted with rofecoxib versus NSAIDs was $0.81 per day, representing an 85% offset of the difference in drug price. For rofecoxib versus NSAIDs, the expected cost per PUB avoided with rofecoxib was $4738, and expected cost per year of life saved was $18,614. In analyses based on endoscopic data, therapy with rofecoxib was less expensive than therapy with NSAIDs, regardless of silent ulcer adjustment. Results were most sensitive to prophylactic GI comedication rates, and were robust over a range of model assumptions and costs.
Conclusions: In this analysis based on differences in clinically significant GI events for osteoarthritis patients, cost differences between rofecoxib and NSAIDs were markedly offset by expected cost savings in GI problems and comedications averted with rofecoxib. Costs per year of life saved with rofecoxib versus NSAIDs were well within accepted benchmarks for cost-effectiveness. When endoscopic data alone were considered, rofecoxib was cost savings across all assumptions about silent ulcer rates.
Diagnosis and treatment of nonsteroidal anti-inflammatory drug associated upper gastrointestinal toxicity
2000, Gastroenterology Clinics of North America
Citation Excerpt :
NSAID users take acid-suppressive therapy twice as often as nonusers.62 Of NSAID users, 22% take either H2-receptor antagonists or proton-pump inhibitors.54 Some studies have shown that H2-receptor antagonists accelerate the healing78,93 or prevent the occurrence of duodenal ulcers,93,154 especially if NSAID use is discontinued.
Gastroenterologists and other clinicians need to be informed and vigilant regarding nonsteroidal anti-inflammatory drug (NSAID)–induced gastrotoxicity. NSAID-associated gastropathy is the commonest and most frequently lethal medication toxicity in the United States.⁴⁶ NSAID toxicity results in more than 100,000 hospitalizations and 10,000 to 20,000 deaths in the United States each year.¹³⁷ To place these statistics in perspective, more Americans die annually from NSAID toxicity than from esophageal, gastric, or hepatic cancer.⁹² Gastrotoxicity substantially raises the cost of NSAID therapy: In one study, for every $100 spent on arthritis therapy, approximately $50 was spent on treating adverse gastrointestinal drug reactions.¹³ In this study, the total annual cost of treating gastrointestinal side effects from NSAIDs was estimated at about $4 billion.¹³ Despite the widespread use of NSAIDs, NSAID-associated peptic ulcer disease (PUD) is frequently overlooked and underdiagnosed because of the asymptomatic presentation of early disease and the underreporting of nonprescription NSAID use.³⁸
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Pharmaceutical Economics & Health PolicyManagement of NSAID-induced gastropathy: an economic decision analysis

Abstract

J Clin Epidemiol

Prim Care

Am J Med

Am J Med

Lancet

Am J Med

A review of selected newer nonsteroidal anti-inflammatory drugs

Am Fam Phys

Nonsteroidal anti-inflammatory drugs and the gut

South Med J

Misoprostol coadministered with diclofenac for prevention of gastroduodenal ulcers. A one-year study

Dig Dis Sci

Nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer disease in elderly persons

Am J Epidemiol

Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study

Arch Intern Med

Nonsteroidal anti-inflammatory drug-induced gastrointestinal injury

Am J Med

FDA's NSAID class labeling estimate of 4–6% GI adverse reaction annually is not valid, PMA maintains: PMA proposes industry-consensus NSAID label warning

FDA Reports

Toward an understanding of NSAID-related adverse events: The contribution of longitudinal data

Scand J Rheumatol

NSAID-associated gastrointestinal damage and the elderly

Pract Gastroenterol

Assessing and understanding patient risk

Scand J Rheumatol

Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs

Ann Intern Med

Double-blind, double-dummy endoscopic comparison of the mucosal protective effects of misoprostol versus ranitidine on naproxen-induced mucosal injury to the stomach and duodenum in rheumatic patients

Am J Gastroenterol

Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: A prospective, double-blind, multicenter study

Am J Gastroenterol

Drug Utilization Evaluation of Michigan Medicaid claims database (12/1/94–11/30/95)

Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials

Arch Intern Med

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: Controlled trial of ranitidine

BMJ

Pharmaceutical Economics & Health Policy
Management of NSAID-induced gastropathy: an economic decision analysis