The prevalence of patients with rheumatoid arthritis in the West Midlands fulfilling the BSR criteria for anti-tumour necrosis factor therapy: an out-patient study

C.-S. Yee, A. Filer1, A. Pace2, K. Douglas3, D. Situnayake4 and I. F. Rowe on behalf of the West Midlands Rheumatology Services and Training Committee

Dudley Guest Hospital, Dudley,
1 Worcestershire Royal Hospital, Worcester,
2 Cannock Chase Hospital, Cannock,
3 Walsgrave Hospital, Coventry and
4 City Hospital, Birmingham, UK


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Objectives. There are currently two anti-tumour necrosis factor (anti-TNF) therapies licensed for treatment of rheumatoid arthritis (RA). A British Society for Rheumatology (BSR) working party defined criteria for patients that would be suitable for such treatment. The aim of this study was to determine the prevalence of these patients attending rheumatology out-patient departments across the West Midlands.

Methods. Data were collected over a 2-week period in adult out-patient departments of 12 centres. A questionnaire was completed at each patient review. Disease activity scores (DAS-28) were recorded for those who had failed methotrexate treatment and at least one other disease-modifying anti-rheumatic drug (DMARD) in the absence of contraindications to anti-TNF therapy. Information was also collected on the number of DMARDs failed and the use of steroid therapy.

Results. A total of 1441 patients with RA were assessed; 177 (12.3%) patients had failed methotrexate and at least one other DMARD. Of these, 19 had contraindications to the use of anti-TNF therapy. In the remaining 158 patients (11%), 80 (5.6%) had a DAS-28 score of >5.1, thus fulfilling BSR criteria for use of anti-TNF therapy. Those with a DAS-28 score of ≤5.1 were significantly more likely to have been taking steroids compared with those with a DAS-28 score >5.1 (68.2 and 49.3%, respectively, P=0.024).

Conclusions. Of patients with RA attending adult rheumatology out-patient clinics in the West Midlands, 5.6% would meet BSR criteria for use of anti-TNF therapy. Eligibility may be affected by steroid use.

KEY WORDS: Rheumatoid arthritis, Out-patients, Anti-TNF therapy, BSR guidelines.


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Rheumatoid arthritis (RA) is characterized by poor treatment outcomes and significant chronic disability [1] with a major financial impact, incurring annual costs in the UK estimated to be in excess of £1billion [2]. With efficacy surpassing currently available disease-modifying anti-rheumatic drugs (DMARDs) and early evidence suggesting a good safety profile, anti-tumour necrosis factor (anti-TNF) therapies offer many patients with severe or refractory RA the possibility of significant clinical and functional improvement [310]. A working party of The British Society for Rheumatology (BSR) established guidelines for the use of anti-TNF therapy, updated in April 2001 [11]. The National Institute for Clinical Excellence (NICE) has adopted these criteria in its guidelines for the use of infliximab and etanercept in RA [12].

Anti-TNF therapies currently cost in excess of £8000 per patient annually. Therefore, in order to plan the organization of both clinical and financial resources in a climate of increasing demands on the NHS, clinicians and purchasers require access to a precise estimate of the prevalence of patients with RA suitable for anti-TNF therapy. Such data will facilitate commissioning primary care trusts and secondary care providers to provide realistic estimates of the cost of treating existing cases. The purpose of this study was therefore to determine the prevalence of patients with refractory RA eligible for anti-TNF therapy according to BSR criteria in the West Midlands region. This region has a population of 5.3 million, served by 38 consultant rheumatologists in 14 centres. In addition, information was collected on the number of DMARDs failed and corticosteroid usage in this group of patients.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Across the West Midlands, 12 centres including 32 rheumatologists agreed to take part in the study during the summer of 2001. Subjects were adults fulfilling American College of Rheumatology criteria for RA attending routine follow-up out-patient appointments in rheumatology departments. Both doctor-led and nurse-led clinics were included. A standard questionnaire attached to the notes of each patient was completed by the attending doctor or clinical nurse specialist. For patients who had failed to respond to methotrexate and one other DMARD according to the BSR criteria, the past history of DMARD use, presence of contraindications for anti-TNF therapy and current steroid use were recorded. For those patients with no contraindications to anti-TNF therapy, simplified 28-joint counts and patient's global assessment of disease activity (100-mm visual analogue scale) were recorded. An erythrocyte sedimentation rate was arranged if none was available within the previous 4 weeks. The patient's use of steroids, whether regular oral or given parenterally within the previous 4 weeks, was also recorded for this group of patients.

Data were collected prospectively over a 2-week period in each centre, then collated centrally. A disease activity score (DAS-28) [13] was calculated for appropriate patients. Statistical analysis was performed using the {chi}2-test; a P value of less than 0.05 was considered statistically significant.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
A total of 1441 patients with RA were assessed, of which 26% were assessed in nurse-led clinics; 72.2% were females and the mean age was 56.7 yr (range: 19–92 yr). The majority were Caucasian (85.5%); 7.1% were Asian, 0.7% Afro-Caribbean and 0.3% other ethnic groups (6.4% unknown). Three patients seen during the course of the study were already established on anti-TNF therapy. Use of combination DMARD therapy was highly variable throughout the region: rates varied from 0% to over 90%, reflecting the different practice of individual centres.

Of 233 patients failing methotrexate treatment, 30.5% were owing to lack of effect and 61.4% because of side-effects or toxicity (8.2% gave no reason); 177 (12.3%) patients had failed methotrexate and at least one other DMARD according to BSR criteria (Fig. 1Go). Of these, 19 had contraindications to anti-TNF therapy. In the remaining 158 (10.7%) patients, only 80 patients had high disease activity as defined by a DAS-28 score of >5.1. The prevalence of patients with RA attending adult rheumatology out-patient clinics in the West Midlands satisfying the BSR criteria for anti-TNF therapy was 5.6%, eligibility being 8.6 and 4.5% in nurse-led and doctor-led clinics, respectively.



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FIG. 1. Schematic of the BSR criteria for anti-TNF therapy which formed the basis for the clinic questionnaire showing numbers of patients assessed at each stage, with percentage of total patients with RA shown to the right. ACR, American College of Rheumatology.

 
Number of failed DMARDs
In the group of 80 patients who satisfied BSR criteria for anti-TNF therapy, 18 (22.5%) had failed one DMARD other than methotrexate, 21 (26.3%) had failed two other DMARDs, 13 (16.3%) had failed three other DMARDs and 28 (35.6%) had failed more than three other DMARDs. Using these data it is possible to assess the impact of changing the criteria for anti-TNF therapy in terms of the number of DMARD therapies required to be failed. The percentage eligible for therapy drops with each additional DMARD required as shown in Table 1Go.


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TABLE 1. Effect of changing the threshold criteria for anti-TNF therapy by increasing the number of DMARDs required to be failed

 

Usage of corticosteroids
Data on usage of steroids were obtained for those patients who had failed methotrexate and at least one other DMARD in the absence of contraindications to anti-TNF therapy. Of patients with a DAS-28 score of ≤5.1, 22 (32%) were taking prednisolone at a dose of <7.5 mg daily compared with seven (9%) with a DAS-28 score of >5.1 on the same dosage. This difference accounted for the overall finding that patients with DAS-28 scores of ≤5.1 were significantly more likely to have been taking steroids compared with those with DAS-28 scores >5.1 (68.2 and 49.3%, respectively, P=0.024), although this effect was not seen for patients on higher steroid doses.


    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
This study is the largest of its kind to derive a percentage prevalence figure for eligibility to biological therapy and its regional design minimizes the effects of divergent clinical practices, referral patterns and local populations, biases to which earlier and smaller studies may have been vulnerable [14]. Collection of data over a 2-week period has the advantage of maximizing response rate amongst a large number of clinicians, and makes it unlikely that patients will be recorded more than once. This also allowed us to achieve our aim of measuring point prevalence at a time before biological therapy became generally available. The study was not intended to address the issue of incident cases. The principal limitation of this study is an inherent selection bias towards patients with greater disease activity; first through collecting data from clinics which by their nature see patients with active disease more frequently, and second through collecting data from clinical nurse specialist clinics, which bias towards less well-controlled patients. In contrast, confining the study to out-patient departments results in negative bias by excluding small numbers of in-patients with very active disease.

Variations in local funding may restrict availability of newer therapies to patients refractory to multiple DMARDs. We therefore included data showing the effect of tightening the criteria by increasing the number of DMARDs to be failed (Table 1Go) in order to illustrate the effects of possible local rationing or ‘postcode prescribing’.

Considerable variation was seen in the use of combination DMARD therapy between different units, hence we have not further analysed its use as a potential criterion for anti-TNF therapy. Furthermore, as our study showed that over 60% of patients failed methotrexate therapy owing to side-effects or toxicity, a significant proportion of patients would be excluded from use of evidence-based combination therapy with methotrexate [15, 16]. We would therefore suggest that the introduction of criteria requiring the use of combination therapy would be inappropriate in the light of current practice.

There is a concern that treatment with steroids may mask disease activity in some patients; it is therefore relevant to assess eligibility in the light of steroid usage. Though our data regarding the use of steroids in criteria-fulfilling patients appear to show a tendency towards masking of activity, the significance of this remains unclear, as the difference was within the group taking less than 7.5 mg prednisolone daily and not with higher doses.

An alternative approach to estimating eligibility while avoiding selection bias is to obtain figures from community population-based studies, deriving percentage eligibility from measures of disease severity and estimates of proportions attending secondary care clinics. This type of estimate, utilizing data from the Norfolk Arthritis Register, was used in the clinical and cost-effectiveness assessment commissioned by NICE for their guidance on the use of infliximab and etanercept in adults [12]. Both approaches require that certain assumptions be made in order to arrive at estimates of eligibility. However, it is of interest to compare the results obtained if these estimates are extrapolated to provide a figure of eligibility per 100 000 population. Assuming 80% of patients with RA attend secondary care clinics [17], our study gives a figure of 35.8/100 000 population who would be eligible for anti-TNF therapy. This is in excess of the source data used by NICE, which if extrapolated give a figure of 24.2/100 000 allowing for patients with contraindications.

Following the adoption of the BSR criteria by NICE, our figures provide further information for use by commissioning primary care trusts and secondary care providers to estimate the cost of treating existing cases from data on local population or secondary care clinic sizes. Further studies at local or regional level could assess the impact of wider availability of biological therapies and also of incident cases.


    Conflict of interest
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
The authors have declared no conflicts of interest.


    Acknowledgments
 
We would like to thank the patients and professionals from the following centres who were involved in this study: City Hospital NHS Trust, Dudley Group of Hospitals NHS Trust, George Eliot Hospital NHS Trust, North Staffordshire Hospital NHS Trust, Birmingham Heartlands and Solihull NHS Trust, Hereford NHS Hospitals Trust, Mid-Staffordshire General Hospital NHS Trust, Royal Wolverhampton NHS Trust, Sandwell Healthcare NHS Trust, Walsall Hospitals NHS Trust, University Hospital Birmingham NHS Trust, University Hospital Coventry and Warwickshire NHS Trust and Worcestershire Acute Hospitals NHS Trust.

We would also like to thank the following colleagues who helped directly in organizing the study across the region: Drs H. Ali, M. Allen, N. Amft, J. Barber, S. Bowman, R. Callaghan, D. Carruthers, G. Chelliah, J. S. Coppock, T. J. Constable, P. Dawes, J. Delamere, C. Dowson, R. Duncan, N. Erb, A. A. Faizal, C. Gordon, K. Grindulis, A. Hassell, E. Hay, A. Jordan, R. Jubb, S. Kamath, F. Khattak, G. Kitas, D. Mulherin, P. Newton, R. Palmer, A. Paul, P. Perkins, T. Potter, A. Prabu, T. Price, A. Price-Forbes, M. Pugh, A. Rai, E. Rankin, D. Rees, M. P. Shadforth, T. Sheeran, G. Struthers, A. Whallett and R. Williams.


    Notes
 
Correspondence to: I. F. Rowe, Worcestershire Royal Hospital, Charles Hastings Way, Worcester WR5 1JG, UK. E-mail: ian.rowe{at}worcsacute.wmids.nhs.uk Back


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 

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Submitted 10 July 2002; Accepted 3 December 2002