Rheumatology Advance Access originally published online on June 19, 2007
Rheumatology 2007 46(8):1379-1380; doi:10.1093/rheumatology/kem142
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Reply: Adalimumab-associated pulmonary fibrosis
Department of Medicine, Queen Elizabeth Hospital, Sheriff Hill, Gateshead NE9 6SX, UK
Correspondence to: Dr C. KELLY. E-mail: clive.kelly{at}ghnt.nhs.uk
SIR, We enjoyed reading the letter from Huggett and Armstrong in the October issue of the journal [1], and agree that their case report adds to the mounting body of evidence that suggests that most, if not all, anti-tumour necrosis factor (TNF) drugs may precipitate sudden, severe and often fatal respiratory failure in patients with rheumatoid arthritis (RA). However, we believe that it also highlights the importance of understanding which patients are at greatest risk of this development. The case described [1] had a normal chest radiograph prior to commencing adalimumab but a CT scan <3 months into treatment showed clear evidence of established interstitial pulmonary fibrosis with honeycombing in both lung bases. This pattern is typical for interstitial pulmonary fibrosis (IPF) complicating RA itself [2] and is most unlikely to have developed exclusively over the 2 weeks of symptomatic dyspnoea prior to presentation. This strongly suggests that pulmonary disease was established prior to the commencement of anti-TNF therapy.
Most patients on anti-TNF therapy (but not all on adalimumab) are co-prescribed methotrexate, which itself may of course precipitate acute pneumonitis. This is also more likely to occur in the context of pre-existing IPF [3]. In this context, it is important to note that the BSRBR has reported a 2 fold increase in the incidence of clinically apparent respiratory disease in RA patients on anti-TNF agents when compared with the ‘control’ group on methotrexate alone.
Gross reduction in gas transfer is typical of advanced IPF and is a much more sensitive marker of this condition than a pre-treatment chest X-ray. We fully agree with the authors that caution should be exercised with all anti-TNF drugs in treating RA patients with prior lung disease, but would exhort colleagues to consider pulmonary function testing if there is clinical concern about IPF, as a chest X-ray alone may provide false reassurance. If pulmonary function is significantly reduced (vital capacity or gas transfer <70% predicted) then a high-resolution CT scan is indicated to define the cause. The presence of IPF (or established bronchiectasis) should then be considered a relative contraindication to proceeding with anti -TNF therapy [4].
The authors have declared no conflicts of interest.
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- Huggett MT, Armstrong R. Adalimumab associated pulmonary fibrosis. Rheumatology (2006) 45:1312–3.
[Free Full Text] - Ed. Clive Kelly. Lung disease in rheumatic disorders. Baillieres Clinical Rheumatology (1993) 7:1.[CrossRef][ISI]
- Howse M, Tose J, White C, Kumar N, Heycock C, Kelly CA. Can baseline pulmonary function tests predict pulmonary toxicity in patients receiving methotrexate for rheumatoid arthritis? Internal Medicine (1999) 7:51–4.
- Saravanan V, Kelly CA. Drug related pulmonary problems in patients with rheumatoid arthritis. Editorial Rheumatology (2006) 45:787–90.
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