Anti-tumour necrosis factor therapy in the West Midlands

D. Bartram, T. Sheeran, T. Price and D. Mulherin

Department of Rheumatology, Cannock Chase Hospital, Brunswick Road, Cannock, Staffordshire WS11 2XY, UK

Correspondence to: D. Mulherin. E-mail: diarmuid.mulherin{at}msgh-tr.wmids.nhs.uk

SIR, The recent paper by Yee et al. [1] has provided valuable information about the potential uptake of anti-tumour necrosis factor (TNF) therapy by patients with rheumatoid arthritis in the West Midlands. Since this regional audit, of which we were part, the National Institute for Clinical Excellence (NICE) published guidelines for the use of infliximab and etanercept in March 2002 [2]. These biologic therapies are now increasingly prescribed, but with variable local constraints on their use, so-called ‘post-code’ prescribing [3]. At Cannock Chase Hospital rheumatology department, which provides rheumatology care to 500 000 people in the West Midlands, we were one of the biggest initiators of anti-TNF therapy in the country in the months after NICE issued its guidance. In April 2003, we completed an audit of all patients who had started this therapy in the 6 months from April 2002 and believe the results give further practical depth to the necessarily more theoretical audit of Yee et al.

Forty-one patients (24 female), median (range) age 59 (21–74) yr commenced anti-TNF therapy in the 6-month period after 1 April 2002. All had ‘continuing clinically active rheumatoid arthritis that had not responded adequately to at least two disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate’ [2]. Median (range) disease activity score (DAS) was 6.46 (5.05–8.63) prior to initiation of anti-TNF therapy [4]. All commenced therapy with infliximab at 3 mg/kg per infusion, because etanercept was unavailable. In 34 patients, methotrexate was co-prescribed; other DMARDs or oral corticosteroids were co-prescribed with infliximab to those patients who could not tolerate methotrexate. A repeat DAS was measured at least 3 months after therapy was initiated in 36 patients; three patients had stopped therapy before a repeat DAS was measured and two patients did not have a repeat DAS. Thirty-one patients had a fall in DAS >1.2 with nine patients achieving remission (DAS <3.2). Seven patients had discontinued therapy by the time of this audit owing to sepsis in two (unresolving digital infection, presumed bacterial endocarditis), allergic drug reactions in three (skin rash and/or anaphylaxis), increased fits in a patient with previously stable epilepsy, and severe left ventricular failure in one. In most of these patients with side-effects, there was no clear benefit in continuing the therapy and the side-effects were the ‘last straw’ which precipitated discontinuation.

The National Institute for Clinical Excellence has suggested that a unit of our size might expect to have about 150 eligible patients [2]. Our experience with the first ‘quarter’ of these has highlighted various practical difficulties. Early shortages of etanercept created a heavy burden on already stretched rheumatology day-care facilities. Co-prescription of methotrexate with infliximab was not always possible and in the absence of alternative anti-TNF therapies, alternative immunosuppression was used—the availability of other therapies should now remove the need for this off-licence practice. Logistical issues make it difficult to monitor the response to these expensive therapies comprehensively—this audit has identified that two of our patients did not have a repeat DAS. Securing adequate staffing levels to identify suitable patients, administer the treatment and monitor the response is an ongoing issue within our local health economy. There is no clear guidance from NICE on the appropriate action if a patient does not respond to infliximab at 3 mg/kg—there is a growing belief that the dose and frequency of administration of this drug may need to be increased in some patients, but at considerable extra cost. Discontinuation owing to side-effects or inefficacy occurred in 17% of our patients, somewhat less than the 40% suggested by NICE, but this may reflect the shorter period of follow-up in this audit. Our experience of infection in these patients has been less worrying than that reported recently by Moots et al. [5] but, again, the patients have been followed over a relatively short period. Time will tell if the early promise of anti-TNF therapies is delivered and whether important practical differences will emerge between the competing drugs in this arena, which will influence clinical practice.

The authors participated in clinical trials involving infliximab and obtained ‘free’ infliximab for patients on compassionate grounds prior to its wider availability.

References

  1. Yee CS, Filer A, Pace A, Douglas K, Situnayake D, Rowe IF. Rheumatology 2003;42:856–9.[Abstract/Free Full Text]
  2. National Institute for Clinical Excellence. Guidance on the use of etanercept and infliximab for the treatment of rheumatoid arthritis. London: NICE, 2002.
  3. Arthritis and Musculoskeletal Alliance. Press Release: Access to treatments still denied to people with rheumatoid arthritis. London: ARMA, 2003 (available at www.msecportal.org/portal/editorial/PublicPages/bsr/536883279/ARMASurveyPressRelease.doc)
  4. 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]
  5. Moots R, Taggart A, Walker D. Biologic therapy in clinical practice: enthusiasm must be tempered with caution. Rheumatology 2003;42:614–6.[Free Full Text]
Accepted 2 September 2003





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