Infections and anti-TNF therapy: strategies for screening based on clinical experience

C. Estrach1, V. E. Abernethy2 and J. K. Dawson2

1Department of Rheumatology, Countess of Chester Hospital, Chester and 2Department of Rheumatology, St Helens Hospital, St Helens, UK

Correspondence to: C. Estrach, 28 Woodale Close, Whittle Hall, Warrington WA5 3GL, UK. E-mail: estrach{at}belloso.freeserve.co.uk

SIR, We read with interest the article by Kroesen et al. [1] and the editorial by Moots et al. [2]. Both papers highlight the need for awareness of severe infections in patients on anti-tumour necrosis factor (TNF) therapy and the importance of developing strategies to prevent such events.

In our region we encountered a high percentage of serious infections when starting to use these therapies in our patients. Initially in one health authority we had four life-threatening pneumonias out of 20 patients on etanercept [3]. In the 12 months after the pneumonia, three patients died from infections (the mortality rate was 15% in these 20 patients). Interestingly, all the patients had underlying chest disease, not all of them were diagnosed before etanercept therapy, and in particular none of these patients had a previous history of recurrent infections. All of them fulfilled the British Society for Rheumatology (BSR) guidelines for the introduction of biological therapy. Following the development of pneumonia, our patients seemed increasingly prone to severe chest infections, and it seems that pneumonia whilst on anti-TNF therapy may have converted at least one of the patients from asymptomatic to symptomatic bronchiectasis.

Reviewing pivotal anti-TNF trials, the rate of hospitalization with infections is less than 3% [4], but the exclusion criteria are unclear and not easily available for scrutiny. We cannot be sure of the exact nature of the screening process that the participants underwent, and it is now known that in the postmarketing use of these drugs the incidence of infections has been higher than in the trials [5, 6].

The fact that our patients all had underlying chest disease led us to believe that pre-screening should be more intensive. Recent studies suggest that patients with rheumatoid arthritis will have a higher risk of suffering subclinical bronchiectasis and pulmonary fibrosis [7, 8]. Whilst we cannot prevent upper respiratory chest infections, we can try to investigate for underlying chest pathology before starting biological therapies. A detailed chest history, sputum production, frequency of antibiotics, chest examination and chest X-ray should be compulsory. High-resolution computed tomography of the chest should be requested if there is a history of chronic or large volumes of sputum to investigate for bronchiectasis or if pulmonary fibrosis is suspected [7, 8]. The cost of this screening is negligible compared with the cost of anti-TNF therapy and prolonged hospital stays. The presence of bronchiectasis is highly likely to influence our decision on whether to commence anti-TNF therapy.

Following our initial experience, we have been screening our patients more intensively. A proforma for the assessment of candidates has been developed and is now used across the region. This includes the basic BSR guidelines but also a detailed infection and antibiotic history, sputum volume, chest X-ray and the results of relevant further investigations when indicated.

The experience so far is minimization of the chest complications and a higher degree of awareness of chest symptoms. The trend is for nurses to run most of the anti-TNF clinics in the country, and good, clear, user-friendly forms are a useful way of ensuring the right selection of patients and unification of education and monitoring.

More recently an anti-TNF support group has been created in our region, including everybody (doctors and nurses) involved in the day-to-day running of biological clinics, where it is possible to update knowledge and protocols and to share experiences in order to maximize patient safety.

The authors have declared no conflicts of interest.

References

  1. Kroesen A, Widner F, Tyndell A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF{alpha} therapy. Rheumatology 2003;42:617–21.[Abstract/Free Full Text]
  2. Moots R, Taggart A, Walker D. Biologic therapy in clinical practice: enthusiasm must be tempered by caution. Rheumatology 2003;42:614–16.[Free Full Text]
  3. Estrach C, Moots RJ, Andrews S, Williams D, Sykes HR, Dawson JK. High incidence of pneumonia in patients on anti-TNF therapy. Rheumatology 2002;41(Suppl. 1):93.
  4. Moreland LW, Schiff MH, Baumgartner SW et al. Etanercept therapy in rheumatoid arthritis: A randomized, controlled trial. Ann Intern Med 1999;130:478–86.[Abstract/Free Full Text]
  5. Baghai M, Osmon DR, Wolk DM et al. Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept. Mayo Clin Proc 2001;76:653–6.[ISI][Medline]
  6. Smith D, Letendre S. Viral pneumonia as serious complication of etanercept therapy. Ann Intern Med 2002;136:174.[Free Full Text]
  7. Despaux J, Manzoni P, Toussirot E et al. Prospective study of the prevalence of bronchiectasis in RA using high-resolution computed tomography. Rev Rheum Engl Ed 1998;65:453–61.
  8. Dawson JK, Fewins HE, Desmond J et al. Fibrosing alveolitis in patients with RA as assessed by high-resolution computed tomography, chest radiography and pulmonary function tests. Thorax 2001;56:622–7.[Abstract/Free Full Text]
Accepted 3 July 2003





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