Lund University Hospital, Department of Rheumatology, S-221 85 Lund, Sweden
SIR, We read with interest the editorial Targeted therapies in rheumatoid arthritis: the need for action [1]. In support of the ideas raised, we would like to report our initial experiences of a clinical protocol for rapid evaluation of the response to new treatment modalities in patients with rheumatoid arthritis (RA).
In Sweden, the new biological anti-tumour necrosis factor drugs infliximab (Remicade) and etanercept (Enbrel) have been available for use in RA since March 1999, provided that permission is granted for the individual patient by the Medical Products Agency. The requirements are that the patient has established active RA which is not responding to at least two disease-modifying anti-rheumatic drugs (DMARDs), and that standardized monitoring is provided. Thus we were offered a unique opportunity to test the hypothesis that a standardized clinical protocol can yield rapidly available, useful, early information about the efficacy and other features of new anti-rheumatic drugs. This could reveal information not apparent in clinical trials, which do not always reflect the performance of the drug in real life [2]. Furthermore, since two novel drugs with the same principal cytokine target had become available, we also wanted to be able to compare these drugs in the population of patients we see in our daily practice, i.e. patients selected on the basis of current disease activity but with very different backgrounds concerning previous treatment, concomitant diseases and functional impairment and disability.
The patients are evaluated at initiation of treatment, at week 2 and week 6, and thereafter every 3rd month for Enbrel and every 2nd month for Remicade, to comply with the administration regimens. The evaluations are performed immediately before a new infusion/injection. At initiation and at the follow-up evaluations the mean weekly dosage for the previous 2 weeks of the biological treatment is recorded. Concomitant treatment with DMARDs, oral glucocorticoids, the numbers of swollen and tender joints (28-joint count), pain [visual analogue scale (VAS)], patient's overall assessment (VAS), physician's global assessment (five grades), erythrocyte sedimentation rate and C-reactive protein are recorded. The number of intra-articular glucocorticoid injections administered, any unforeseen medical observations, permanent and temporary drug withdrawal, surgical operations, and drug side-effects since the last measuring point are recorded.
To improve the quality of the data on the forms, these are thoroughly evaluated before the data are entered into the computer. A computer application has been developed for data handling (PC, MS Access). The application calculates disease activity score (DAS28) [3] and the following response criteria: American College of Rheumatology (ACR) 20, ACR 50, European League Against Rheumatism (EULAR)/WHO 20, EULAR/ WHO 50, that is 20 or 50% improvement compared with the values at inclusion [4, 5]. These validated response criteria are compared with the improvement in DAS28, reduction in Health Assessment Questionnaire score and reduction in oral prednisolone by 20 and 50%. For the individual patient, a graphical representation of the measured variables over time and a calculation of the extent of their fulfilment of the different response criteria are presented to the treating physician within 24 h as a tool for treatment decisions (Fig. 1). For the whole patient cohort, the application can plot graphically the mean values of the variables over time and the percentages of patients fulfilling the different response criteria. These data are presented to the rheumatologists at regular intervals to encourage participation by all clinicians.
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Our experience to date includes all patients treated with either Enbrel or Remicade at the Department of Rheumatology at Lund University Hospital. So far, 74 patients have commenced treatment with Enbrel. Forty-one of these have been monitored for at least 3 months. Only 10 patients are being treated with Remicade and six of these have been treated for 3 months. The patient characteristics are shown in Table 1.
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In Sweden, the social security system allows therapeutic decisions to rely heavily on the estimated medical need and the economic status of the patient does not influence treatment decisions. However, due to the profound influence on the economy of the medical system of these treatment principles, it is extremely important to be able to document the costbenefit ratio of the introduction of these drugs to prove their utility also from a health economics perspective. Accordingly, the protocol also includes a socioeconomic part, which includes a survey of the working/sick leave status, surgery, and hospitalization, as well as the generic instruments EuroQol and the Nottingham Health Profile.
The immediate feedback to the treating physician, with graphical presentation of the measured variables as well as information about the fulfilment of the response criteria, has been well received by the staff and is considered very helpful in the care of these patients. The rapid and powerful on-line presentation of the therapeutic response has made the system attractive to a number of regional rheumatological centres. Patients from these centres are now being included in the database.
This system for monitoring the effects of targeted therapies in clinical practice can easily be applied also in monitoring the effects of conventional DMARDs. The computer-assisted system offers rapid and convenient feedback of treatment results to the physician as well as easy access to up-to-date compilations of treatment results for all patients or subgroups of patients. We believe that our system represents a significant step towards the fulfilment of some of the requirements outlined in the editorial [1]. Thus, it is possible to evaluate the effects of therapy, define strict criteria for efficacy/inefficacy, and evaluate each patient accordingly and measure the worsening of symptoms after withdrawal of the drug in a standardized fashion. The system also facilitates the creation of regional immunotherapy centres, where the data base may be centralized and give rapid feedback to each participating unit. The units do not necessarily require the computer facilities, but the system ensures that the drugs are administered according to strict criteria and monitored uniformly.
We fully agree with the authors of the editorial that there is an urgent need for action by rheumatologists in order to ensure that novel treatment modalities are being offered to patients who are in most need of such treatments, at the lowest possible risk and at a cost acceptable to the providers. This will be possible only by careful monitoring of treatment effects on all aspects of the disease. The system presented should be a useful tool in these efforts.
Notes
Correspondence to: P. Geborek.
Accepted 30 March 2000
References
Leeds Teaching Hospitals, Leeds,
1 Guy's Hospital, London,
2 Royal Infirmary, Glasgow and University Hospital of Wales, Cardiff, UK
The authors are to be congratulated on undertaking an effectiveness study of the new anti-TNF therapies. They demonstrate the value of monitoring by experienced physicians and the study will provide information on the effectiveness and withdrawal rate of these drugs. Furthermore, it will allow economic modelling, which is crucial if these drugs are to be made available via State funding.
The potential to monitor conventional DMARDs is also of great interest and we look forward to further information on this system.
Notes
Correspondence to: P. Emery, University of Leeds, 36 Clarendon Road, Leeds LS2 9JT, UK.
Accepted 30 March 2000