Pharmacoeconomic analyses have become useful and essential tools for health care decision makers who increasingly require such analyses prior to placing a drug on a national, regional or hospital formulary. Previous health economic models of non-steroidal anti-inflammatory drugs (NSAIDs) have been restricted to evaluating a narrow range of agents within specific health care delivery systems using medical information derived from homogeneous clinical trial data. This paper summarizes the Arthritis Cost Consequence Evaluation System (ACCES)--a pharmacoeconomic model that has been developed to predict and evaluate the costs and consequences associated with the use of celecoxib in patients with arthritis, compared with other NSAIDs and NSAIDs plus gastroprotective agents. The advantage of this model is that it can be customized to reflect local practice patterns, resource utilization and costs, as well as provide context-specific health economic information to a variety of providers and/or decision makers.

Rheumatic diseases are among the oldest diseases recognized. The classification of rheumatic diseases is sometimes difficult due to unknown aetiology and heterogeneity in their clinical presentation. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common rheumatic diseases, accounting for a large percentage of disability worldwide. The economic and social burden of these diseases is great. Their impact on both individuals and society results from a decreased quality of life, lost productivity and increased costs of health care. Without appropriate approaches to patient management and control of these diseases, this impact can be expected to increase as the population ages. One of the challenges in studying OA and RA, and rheumatic diseases in general, is deriving epidemiological data that can be used to understand better the factors that contribute to the initiation and progression of these diseases. Only with such an understanding can significant progress be made in the diagnosis, treatment and management of patients.

Pharmacoeconomics and pharmacoeconomic models are increasingly being used to guide health care decisions. In designing and using these models, an appropriate balance must be struck between scientific rigour and model transparency. It is therefore important to consider carefully how the various model components, such as model perspective, internal and external validity, and choice of comparators and outcomes, should be integrated into the model. These factors are discussed in relation to the pharmacoeconomic evaluation of non-steroidal anti-inflammatory drugs.

Celecoxib is the first COX-2-specific inhibitor approved for relief of the signs and symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA), as well as for treatment of familial adenomatous polyposis. For both OA and RA, celecoxib has been shown to be significantly superior in efficacy to placebo and similar in efficacy to traditional non-steroidal anti-inflammatory drugs. Its advantage, however, is its gastrointestinal (GI) safety. Randomized clinical trials as well as long-term outcomes studies have demonstrated that the GI safety profile of celecoxib is superior to that of traditional NSAIDs and similar to that of placebo. Additionally, the renal and cardiovascular safety of celecoxib has also become apparent, as well as its efficacy, tolerability and safety in the elderly population.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and used, especially to treat patients with osteoarthritis and rheumatoid arthritis. Since their introduction as a therapeutic class, a large body of literature has accumulated on the side-effects of these drugs. NSAIDs, through their inhibition of prostaglandin synthesis, can affect the renal and cardiovascular systems. However, the majority of reported side-effects are related to the gastrointestinal (GI) system, and the occurrence of these GI events adds significantly to the disease burden. Several factors have been identified that contribute to the risk of an NSAID-associated GI event. However, when considering risk, especially in clinical trials or observational studies, it is necessary to distinguish between baseline risk and NSAID-attributable risk, since this distinction can affect the results and conclusions of the study; NSAID-attributable risk is present in subjects who have few or no risk factors for upper GI toxicity. Safer NSAIDs, such as the new specific cyclooxygenase-2 inhibitors, when targeted to the appropriate patient (i.e. those with NSAID-attributable risk), should lead to improved outcomes and reduced costs.

To report our local experience of the sternoclavicular syndrome and sample the experience of other rheumatologists in the UK.

Osteoporosis is a problem that is relevant to public health from the clinical, economic and social viewpoints. Except in a handful of industrialized countries, there is a considerable void in our knowledge of the magnitude of the problem. By exploring both the epidemiological and the economic impact of osteoporosis and the fractures associated with it in a particular country, studies of the 'burden of illness' (BOI) can fill that void. BOI analysis raises many questions at both the conceptual and the practical level. The purpose of this paper is to review the methodology underlying analyses of this type, to discuss its limitations and to provide a general format to improve their implementation in the field of osteoporosis. Investigators involved in BOI analysis should be very clear and explicit regarding the methods they adopt, so that studies in different countries can be interpreted and compared appropriately by interested parties.

That certain HLA specificities are associated with predisposition to autoimmune disease does not necessarily imply that self-reactive T cells restricted to particular HLA alleles are eliciting the disease. In the present essay, we argue that HLA can be a major genetic factor in the development of autoimmune diseases without T cells being primarily involved in its initiation or perpetuation. There is now ample evidence that self-reactive, regulatory T cells can protect against pernicious autoimmunity. Hereafter, we propose that extended HLA haplotypes, such as DQ3-DR4, DQ3-DR9, DQ5-DR1 and DQ5-DR10 in the case of rheumatoid arthritis, predispose to impaired T-cell-mediated immune regulation. The haplotypes associated with impaired regulation are the combination of certain class II alleles and a yet unknown 'amplifier'. In this model, products of the HLA class II region are not involved in the presentation of particular organ-specific autoantigens. Therefore, HLA does not predispose to autoimmune disease per se, but rather fails to provide efficient protection.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that results in progressive functional limitation, physical disability and premature death. RA extracts a considerable economic toll, particularly in terms of indirect costs related to lost productivity and premature mortality. Given these considerations, any therapy for RA that slows or prevents disability would be expected to confer economic benefit. Determination of drug efficacy does not automatically imply economic benefit, however. Establishment of economic benefit requires a rigorous analysis of both the benefits and the total costs of a given therapy The cost of drug therapy, including treatment of side-effects, currently constitutes only 15% of the total direct cost of RA, so it is important to assess other costs in any economic analysis. Common guidelines with regard to methods, units and data treatment are necessary to permit comparison of the economic benefit of different therapies within and across disease states. Such guidelines are being established for economic evaluations of medical interventions in RA. Application of these guidelines to future pharmacoeconomic studies of RA therapy will permit more accurate assessment of the economic benefit of such treatments. Given the current fiscal constraints on health care, demonstration of economic benefit will become an increasingly important factor for drug acceptance.

Several new drugs have recently been introduced for the treatment of rheumatoid arthritis (RA). These include the cyclooxygenase-2 inhibitor, celecoxib, the anti-tumour necrosis factor agents, etanercept and infliximab, and the new disease-modifying anti-rheumatic drug (DMARD), leflunomide. In clinical trials, celecoxib has been shown to be effective for palliation of the signs and symptoms of RA and to have fewer gastrointestinal side-effects than conventional non-steroidal anti-inflammatory drugs. Etanercept and infliximab are indicated for reduction of the signs and symptoms of RA in patients who have failed to respond adequately to previous DMARDs. The clinical success rate in etanercept-treated patients is significantly better than in placebo-treated patients for up to 18 months. Leflunomide is a DMARD with a novel mechanism of action that has been approved as a first-line treatment for RA. Treatment with leflunomide results in significantly greater improvement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression. Agents are currently in development that will be targeted against components of the immune activation and co-stimulatory pathways. These include antibodies directed against the interleukin-2 receptor and blockers of the CD28 and CD40 co-stimulatory pathways. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future.

Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.

The current paradigm for rheumatoid arthritis suggests that persistent synovitis leads to erosive joint damage, progression of which results in functional disability. Studies of X-ray progression followed for 1-9 yr have shown that 40-83% of subsequent progression can be predicted by a combination of prognostic factors such as joint involvement, high levels of C-reactive protein and rheumatoid factor (RF) positivity. There are similar findings for predictors of functional disability in studies followed for 2-15 yr. The most consistent prognostic feature is RF positivity, which is equally important in predicting joint damage and functional disability. Immunoglobulin A RF and the co-presence of RF with anti-keratin or anti-filaggrin antibodies may increase levels of prediction. Added value of genetic predictors over that of RF remains inconclusive. Therefore, therapeutic management should be individualized. Cases with active disease and seropositive RF tests merit aggressive therapy; conversely, cases with little synovitis and seronegative tests require conservative management.

Functional disability and quality of life in rheumatoid arthritis (RA) are key outcomes that determine patients' demand for care, and influence their compliance and satisfaction with treatment. In the past decade, there has been a shift from physician-focused assessment toward methods based on the postulate that patients can better report their perceptions of health impairment. There are several disease-specific and generic instruments available that have proven valuable in outcome testing in RA. While there are several obvious advantages to patient self-assessment, clinicians may be reluctant to adopt these measurements. Functional assessment testing will be easier to implement if physicians have access to computer resources for quantitation of disease outcomes and if normative data can be provided to make interpretation clear. Despite current limited access to computer resources and normative data, functional disability and quality of life assessment of RA should be encouraged in clinical practice because it fosters better patient-physician relations and provides much needed long-term outcome information on drug therapy beyond clinical trials.