TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice: costs and outcomes in a follow up study of patients with RA treated with etanercept or infliximab in southern Sweden.(Review)

Objectives: To evaluate costs, benefits, and cost effectiveness of tumour necrosis factor inhibitor treatment over one year in routine clinical practice.

Materials and methods: At four rheumatology units in southern Sweden treatment of 160 consecutive patients with RA was started with either etanercept or infliximab. The economic analysis was based on 116 patients with complete data who received treatment for at least one year. Details on drug treatment, functional capacity, disease activity, and laboratory values were available during the entire treatment. Information on resource use and QoL was collected at baseline and throughout the first year. The cost effectiveness analysis was based on changes in outcome and costs compared with the year before treatment. Cost per quality adjusted life year (QALY) gained was calculated for the entire sample and for patients with different levels of functional disability.

Results: During the first treatment year direct costs were reduced by 40%, but indirect costs did not change substantially. Patients' QoL improved on treatment--utility increased from an average of 0.28 to 0.65. Assuming that improvement occurred after three months' treatment, the cost per QALY gained is estimated as 43 500 [euro]. If it occurs after six weeks, in parallel with clinical measures, the cost per QALY is 36 900 [euro]. Sensitivity analysis, including all 160 patients, gave an estimated cost per QALY of 53 600 [euro]. The cost per QALY increases for patient groups with less severe disease.

Conclusion: For this patient group, cost effectiveness ratios are within the generally accepted threshold of 50 000 [euro], but need to be confirmed with larger samples.

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Whenever new treatments are introduced, their cost effectiveness has to be estimated from short term data from clinical trials. In chronic progressive diseases, cost effectiveness analysis generally involves estimating long term effects of treatments using disease models that incorporate disease symptoms and progression, as well as effects on costs and patients' quality of life (QoL). In rheumatoid arthritis (RA), a number of general economic models based on epidemiological data and observational studies have been proposed. (1-3) All have shown a clear increase in costs with worsening physical disability, driven to a large extent by loss of work capacity. At the same time, patients' QoL--expressed as utility--has been shown to correlate highly with disease severity. (2 4) Thus, treatments that delay progression could be expected to reduce the burden of RA by reducing some of the resource consumption, as patients remain for a longer time with mild disease, while at the same time increasing their QoL.

Over the past year a number of economic evaluations have been published in different countries, using such models to estimate the cost effectiveness of new treatments in RA based on clinical trials. (5-9) These evaluations have shown that this hypothesis appears indeed correct, although none of the analyses found that savings were large enough to offset the cost of the new treatments. This leads to a number of critical questions: Does the clinical and QoL benefit justify the additional cost from the perspective of society, compared with other uses of these resources? Which patients should receive this treatment? And will the results in clinical practice differ from the clinical trials and early economic evaluation?

The question of whether reimbursement of expensive new treatments should be conditional upon showing similar benefits in clinical practice as in the models used at their introduction has been discussed over the past decade. In some special cases, the authorities have initiated follow up studies or patient registries, or they have urged companies to do so. The most well known case is multiple sclerosis, in particular the risk-sharing agreement between the National Health Service and companies in the United Kingdom. However, such studies are not currently required in any country.

Clinicians, on the other hand, have become increasingly interested in estimating consequences of treatment strategies used. Particularly in Sweden there is a long tradition of creating patient registries and special follow up studies. A nationwide registry for early RA was set up in 1995 and within this registry patients treated with the new biological drugs are currently specifically followed up. Since the introduction of the first biological drug in 1999, a regional observational follow up registry of patients given new treatments such as etanercept and infliximab has been implemented in southern Sweden (SSATG). (10) Currently, this follow up registry includes over 90% of all patients in the area with prescriptions for these new agents.

The current analysis aimed at evaluating RA related costs, benefits, and cost effectiveness of turnout necrosis factor (TNF) inhibitor treatment over one year, and extrapolating the analysis to the second year of treatment.

MATERIALS AND METHODS

Protocol

The development and approval of the clinical protocol has been reported. (10) Four rheumatology centres participated in the present study (Helsingborg, Kristianstad, Trelleborg, and Lund). The centre in Lund recruits patients from primary, secondary, and tertiary care, but patients with RA are mostly recruited from primary care. The protocol was more comprehensive in Lund, recording detailed consumption of anti-TNF drugs and with closer follow up visits during the observation time. The quality control character of this observational study made it a part of the documentation required by the authorities in Sweden, and thus no formal ethical committee approval was required.

Patients

To be eligible for treatment with infliximab or etanercept, patients had to have a diagnosis of RA according to clinical judgment and have failed to respond to, or to be intolerant of, at least two disease modifying antirheumatic drugs (DMARDs), including methotrexate. Patients with any level of functional impairment and disability were offered treatment based on their current disease activity and/or unacceptable steroid requirement as judged by the treating doctor. In agreement with the guidelines of the Swedish Society of Rheumatology, no formal disease activity level other than the doctor's judgment was required and no restrictions on systemic or local glucocorticosteroid administration applied. Treatment of 160 patients with etanercept/infliximab was started between March 1999 and June 2000. Factors influencing choice of drug and dosage have been reported elsewhere. (10) Patients who discontinued treatment were no longer followed up unless they started to receive one of the other study drugs. Only patients who continued to receive anti-TNF treatment for at least one year and had complete 12 month data were included in the current analysis.

Clinical data

At inclusion, age, diagnosis, disease duration, previous and current treatment with DMARDs, and current treatment with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) were recorded. Clinical data recorded …