Review of eight pharmacoeconomic studies of the value of biologic DMARDs (adalimumab, etanercept, and infliximab) in the management of rheumatoid arthritis.
BACKGROUND
Treatment options for the management of rheumatoid arthritis (RA) have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs) to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a).


OBJECTIVE
To assess the medical literature for studies of the economic value of biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and infliximab) used for the management of RA, compared with the traditional DMARDs such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate, azathioprine, leflunomide, and cyclophosphamide.


METHODS
A comprehensive search of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy, cost-effectiveness, or cost-utility studies published in the English language (from 1966 through November 2004). The search terms and/or MeSH (medical subject headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic agents, antineoplastic and immunosuppressive agents. Studies were critically reviewed and quality was assessed using the Quality of Health Economic Studies instrument. Most studies evaluated the use of biologics among RA patients resistant to DMARDs. Studies were assessed with regard to comparators evaluated, measures of efficacy, perspectives, model duration, treatment duration, and discount rate.


RESULTS
From 180 titles identified, 155 were excluded for the following reasons: 89 because they did not consider the drugs of interest, 15 because the population was not RA, 19 because of having the wrong drugs and population, 22 because they were review articles, and 10 because they were general articles. Twentyfive abstracts were accepted for further review. Of these, 13 abstracts were subsequently selected for full-text review. One of the authors identified a study not indexed in MEDLINE. Ultimately, 2 cost-effectiveness and 6 cost-utility studies were selected for this critical review. One study over 6 months reported that triple therapy with DMARDs (methotrexate-hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant patients, which is consistent with American College of Rheumatology (ACR) guidelines that support the use of triple therapy prior to biologics. The incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an ACR20 response for this triple therapy compared with no second-line agent. Overall, biologic therapies cost considerably more than traditional DMARDs but produced more quality-adjusted life-years (QALYs). Despite differences in design and assumptions, published economic models consistently reported ICERs <50,000 dollars per QALY gained for biologics compared with traditional DMARDs, although ICERs of >100,000 dollars were reported from sensitivity analyses.


CONCLUSIONS
Clinical guidelines currently recommend the use of biologics as step therapy after failure of traditional DMARDs. Reported ICERs comparing biologics with traditional DMARDs are within a range that is comparable with other accepted medical interventions. The worth of the additional expenditure will ultimately be judged by formulary and policy decision makers because no maximum cost has been defined. Models can be used to inform decision makers, but they must be interpreted and applied carefully. More research is also needed to differentiate the relative economic value of the various biologic agents by therapeutic indication.
Doan
Quan V
QV
Cerner LifeSciences, 9100 Wilshire Blvd., Suite 605E, Beverly Hills, CA 90212, USA. qdoan@cerner.com
Chiou
Chiun-Fang
CF
Dubois
Robert W
RW
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000191:economics*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000191:economics*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000191:economics*; D003362:Cost-Benefit Analysis; D017850:Economics, Pharmaceutical; D000068800:Etanercept; D006304:Health Status; D006801:Humans; D007074:Immunoglobulin G / Q000191:economics*; D000069285:Infliximab; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D018124:Receptors, Tumor Necrosis Factor; D013548:Sweden; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D006113:United Kingdom; D014481:United States
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept