BMJ  2004;329:1266 (27 November), doi:10.1136/bmj.329.7477.1266

Paper

DRUG POINTS

Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab

¹ Department of Rheumatology, Addenbrooke's Hospital, Cambridge CB2 2QQ, ² Norfolk and Norwich University Hospital, Norwich

Introduction

Tumour necrosis factor (TNF) antibodies are increasingly used to treat autoimmune conditions. However, their long term safety is unclear. We report three cases of patients who developed rapid fatal exacerbations of rheumatoid arthritis associated fibrosing alveolitis after taking infliximab (a chimeric monoclonal anti-TNF antibody; Remicade, Schering-Plough).

Cases

Each patient had longstanding rheumatoid arthritis, was taking azathioprine, and had previously been diagnosed as having asymptomatic fibrosing alveolitis. Sudden onset of breathlessness associated with deteriorating lung function occurred after three or fewer doses of infliximab. Extensive investigations did not find any infection or other cause for the respiratory decline. Details of the patients and investigation are shown in the table.

View this table: [in this window] [in a new window]   Cases of fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab

 

Comment

As the pathophysiology is unknown, we caution the use of infliximab in patients with underlying lung disease. An infection may have caused the deterioration despite lack of isolation of an organism. Vigilance is needed for all patients on immune modulating drugs. Conversely, progressive lung disease may be falsely attributed to an infection when the cause is an inflammatory or idiosyncratic reaction.

Two further cases of pneumonitis associated with infliximab as monotherapy have been reported: one patient with Crohn's disease, the other in a patient with ankylosing spondylitis.^{1 2} Etanercept (a TNF receptor fusion protein; Enbrel, Wyeth) has also been linked with lung injury.³ Cases have also recently been described of infliximab precipitating methotrexate pneumonitis.⁴

Associations of pulmonary disease and all three licensed biological agents for rheumatoid arthritis—infliximab, etanercept, and adalimumab (a humanised monoclonal anti-TNF antibody; Humira, Abbott)—have been reported to the Medicines and Healthcare Products Regulatory Agency.

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We thank A Lim and S Lane for their management of the patients.

Funding: None.

Competing interests: DGIS has received grants from Abbott Laboratories, Schering-Plough, and Wyeth Pharmaceuticals. AJC has received reimbursement for attending a meeting from Abbott Pharmaceuticals. AJKO has received reimbursement for attending symposiums and fees for speaking from Abbott Pharmaceuticals and Schering-Plough.

References

1. Dotan I, Yeshrurn D, Hallak A, Horowitz N, Tiomny E, Reif S, et al. Treatment of Crohn's disease with anti TNF alpha antibodies: experience in the Tel Aviv Medical Center. Harefuah 2001;140: 289-93.[Medline]
2. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359: 1187-93.[CrossRef][ISI][Medline]
3. Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122: 1858-60.[Abstract/Free Full Text]
4. Courtney PA, Alderdice J, Whitehead EM. Comment on methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. Arthritis Rheum 2003;49: 617, author reply 617-8.[ISI][Medline]

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Infliximab and lung disease

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bmj.com, 30 Nov 2004 [Full text]