Background: Treatment with tumour necrosis factor alpha TNF-, or simply TNF ; inhibitors is considered to be an alternative to the use of traditional disease-modifying antirheumatic drugs DMARDs ; in patients with different rheumatic diseases, i.e. rheumatoid arthritis RA ; . There are three TNF-inhibitor drugs currently available on the market brand names in brackets ; : adalimumab Humira ; , etanercept Enbrel ; and infliximab Remicade ; . The Norwegian Knowledge Centre for the Health Services has previously summarised the evidence on the drugs' efficacy and safety in randomised clinical trials and observational studies ; while the present report considers cost-effectiveness of the drugs for rheumatoid arthritis. After considerable growth over several years, the aggregate sales of the three drugs amounted to 860 million NOK in 2006. RA is a serious disease, not least from an economic perspective. No cost-of-illness studies have been found for Norway, but studies from Sweden suggest that the costs of the disease are substantial with a large proportion related to loss of work capacity. Methods: We undertook a review of economic evaluations of TNF-inhibitors against RA, and considered an analysis of health-related quality of life data for patients on TNF-inhibitors and DMARD users from a Norwegian observational study. Results: A total of twelve studies from six countries was included in the literature review. The studies were based on health economic models, which were diverse in their characteristics, and therefore the estimates of cost-effectiveness varied significantly. Conclusions: In our review of economic evaluations of TNF-inhibitors, we found significant variation in the type and features of the models used, which led to a wide range of estimates. The potential for direct comparisons of results between the studies, and thus transferability of results into Norwegian setting, is limited. With this in mind, our main conclusions are as follows: First line therapy: TNF inhibitors seem not to be cost-effective as first line therapy, based on the one study in which this was considered. Second line therapy: We cannot draw any conclusions, since no relevant studies were found. Third line therapy: TNF-inhibitors may be cost-effective, particularly in the case of patients in early disease. The drugs are also likely to be more cost-effective for patients who experience a good rather than a moderate response. Indirect costs: Prevention of productivity loss may account for considerable savings, but has only been accounted for in a few of the economic evaluations. Analysis of six month quality of life data: Data from Norway indicate that RA patients on TNF + methotrexate MTX ; on average experience a larger improvement in health-related quality of life than patients on MTX monotherapy who in turn had a larger improvement than those on TNF monotherapy. Differences in patient groups concerning severity of disease and MTX tolerance should however, be taken into consideration.

Platelet adhesion to collagen type IV. Platelet adhesion to collagen type IV was tested in both the recirculating perfusion system and the single-pass perfusion system. A collagen type IV density of 30 &cm2 resulted in homogenous platelet coverage, consisting of aggregates and occasional single dendritic platelets Fig 2A and B ; . Platelet adhesion was increased with increasing shear rate in both systems Fig 3A and B ; . The percent platelet coverage reached a maximum at a shear rate of 1, 000 s-' in the recirculating perfusion system, whereas the increase in platelet coverage continued u p to shear rate of 2, 000 s-' in the single-pass perfusion system. A sharp, donor-dependent decline above a shear rate of 2, 000 s-', as shown in Fig 3C for the single-passperfusion system, was observed in both systems. Significant differences between both perfusion systems were observed for platelet deposition on collagen type IV at a shear rate of 1, 600 s-' Fig 4 ; . No significant differences were observed between the recirculating and single-pass perfusion systems for platelet deposition o n collagen type I or collagen type 111 results not shown ; . To find an explanation for the increased platelet adhesion. Adalimumab is generally given in combination with methotrexate, but can be given as monotherapy in cases of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate and adriamycin.

Placebo-controlled trial ASSERT ; . Arthritis Rheum 2005; 52 2 ; : 582-91 Baraliakos X, Listing J, Rudwaleit M, et al. Radiographic progression in patients with ankylosing spondylitis after two years of treatment with the tumor necrosis factor-a antibody infliximab. Ann Rheum Dis 2005: 64 10 ; : 1462-6 Haibel H, Brandt H, Rudwaleit M, et al. Efficacy and safety of adalimumab in the treatment of active ankylosing spondylitis: preliminary results of an open-label, 20-week trial. [abstract 454]. Arthritis Rheum 2004; 50 suppl 9 ; : S217 Davis J, Kivitz A, Schiff M, et al. Major clinical response and partial remission in ankylosing spondylitis subjects treated with adalimumab: the ATLAS trial [abstract 483]. Arthritis Rheum 2005; 52 9 suppl ; : S208-9 Mease PJ, Goffe BS, Metz J, et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000; 356 9227 ; : 385-90 Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004; 50 7 ; : 2264-72 Mease P, Gottleib A, Woolley JM, et al. Sustained improvements in patientreported outcomes in psoriatic arthritis patients treated with etanercept [abstract P5]. J Acad Derm 2005; 52 suppl ; : P2 Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial IMPACT ; . Arthritis Rheum 2005; 52 4 ; : 1227-36 Antoni C, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005; 64 8 ; : 1150-7 van der Heijde D, Kavanaugh A.

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