CASE STUDIES - Fatal exacerbation of RA associated fibrosing alveolitis in patients given Remicade

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BMJ 2004;329:1266

27 November

Paper

DRUG POINTS

Fatal exacerbation of rheumatoid arthritis associated fibrosing

alveolitis in patients given infliximab

J K Ostor, locum consultant rheumatologist1, J Crisp,

consultant rheumatologist1, Margaret F Somerville, rheumatology nurse

specialist2, G I , professor of rheumatology2

1 Department of Rheumatology, Addenbrooke's Hospital, Cambridge CB2 2QQ,

2 Norfolk and Norwich University Hospital, Norwich

Correspondence to: A J K Ostor andrew.ostor@...

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.

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.

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.. 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.[Medline]

http://bmj.bmjjournals.com/cgi/content/full/329/7477/1266

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