Dose reduction of etanercept—can we treat more patients using a fixed budget?

G. Clunie, S. Voules and R. Watts

Department of Rheumatology, The Ipswich Hospital NHS Trust, Heath Road, Ipswich, Suffolk IP4 5PD, UK

SIR, Tumour necrosis factor-{alpha} (TNF-{alpha}) blocking drugs (etanercept and infliximab) are effective therapies for rheumatoid arthritis [1, 2]. The introduction of these drugs into routine clinical practice has resulted in considerable pressure on drug budgets and consequent restriction of drug usage. Calculated over 5 yr, the average annual cost of etanercept is £8450 and of infliximab is £6140 for patients who weigh up to 67 kg, up to £9200 for patients who weigh 67–100 kg and up to £12 300 for patients who weigh up to 133 kg. The recommended dose of etanercept is 25 mg delivered by subcutaneous (s.c.) injection twice weekly. In our department we have had, to date, a fixed budget for the use of these drugs. We decided to study whether responses, occurring as a result of taking etanercept for rheumatoid arthritis (RA), could be maintained by increasing the interval between injections.

Patients were considered suitable to receive etanercept if the British Society of Rheumatology (BSR) criteria for inclusion/exclusion were satisfied [3]. Etanercept was started at the recommended dose of 25 mg s.c. twice weekly. An improvement by at least an American College of Rheumatology (ACR) 50 on two consecutive occasions 3 months apart qualified patients to receive advice to reduce the frequency of etanercept injections [4]. All patients therefore had received a minimum of 6 months therapy at the standard dose. A pragmatic approach was adopted. Patients were advised to increase the interval gradually between injections, as they felt able, with the aim of reaching a single injection each week. Assessments were completed by a single observer (SV) every 3 months and included recording an ACR response and disease activity (DAS 28) scores [46]. Ipswich Hospital NHS Trust ethical committee approval was obtained for the study.

Fourteen patients (seven male, mean age 55 yr) have been treated with etanercept for at least 6 months at the standard dose. Patients had received an average of four disease-modifying anti-rheumatic drugs (DMARDs) prior to receiving etanercept. Four patients failed to respond to, or poorly tolerated, the injections and etanercept was discontinued. Ten patients achieved at least an ACR 50 score compared with baseline on two occasions separated by 3 months and were invited to increase the dose interval between etanercept injections. Four patients have subsequently managed to reduce the injections to once weekly; three of whom have maintained an ACR 70 and the fourth an ACR 50 score. Six patients tried but were unable to increase the dose interval between injections without loss of efficacy judged by their own assessment and interpretation of symptoms.

Thus by using a pragmatic patient-centred approach to the dosing of etanercept, it is possible to increase the interval between injections to once weekly without loss of efficacy. This was possible in 40% of patients who responded significantly to etanercept. Halving the dose of etanercept in these patients has enabled us to treat two extra patients at standard doses from our fixed budget. To confirm whether this strategy is associated with a slowing of RA progression, all patients are being monitored closely with appropriate serial radiographs to assess the degree of joint damage over time, compared with patients receiving twice-weekly injections.

This small exercise highlights the potential of investigating varying etanercept dose regimes in treating RA.

Notes

Correspondence to: G. Clunie. E-mail: gavin.clunie{at}ipsh-tr.anglox.nhs.uk Back

References

  1. Weinblatt ME, Kremer JM, Bankhurst AD et al. A trial of Etanercept, a recombinant tumour necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253–9.[Abstract/Free Full Text]
  2. Lipsky PE, van der Heijde DMFM, Clair EW et al. St. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000;343:1594–602.[Abstract/Free Full Text]
  3. Guidelines for prescribing TNF-{alpha} blockers in patients with rheumatoid arthritis. Oxford: British Society of Rheumatology, 2001.
  4. Felson DT, Anderson JJ, Boers M et al. The American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727–35.[ISI][Medline]
  5. Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van der Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8.[ISI][Medline]
  6. van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845–50.[CrossRef][ISI][Medline]
Accepted 16 September 2002





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