RESEARCH - DMARDs and elective surgery in RA: the need for more data

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ls of the Rheumatic Diseases 2004;63:602-603

© 2004 by BMJ Publishing Group Ltd & European League Against Rheumatism

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LETTER

Disease modifying treatment and elective surgery in rheumatoid arthritis:

the need for more data

A Jain1,2, R Maini1 and J Nanchahal3

1 Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College

London, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK

2 Department of Plastic and Reconstructive Surgery, Faculty of Medicine,

Imperial College London, Charing Cross Hospital, Fulham Palace Road, London

W6 8RF, UK

3 Department of Hand and Peripheral Nerve Surgery, University of Sydney,

Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia

Correspondence to:

MrA Jain

AJainUK@...

Accepted 2 February 2004

Keywords: rheumatoid arthritis; disease modifying antirheumatic drugs;

elective surgery

Disease modifying antirheumatic drugs (DMARDs) have become the cornerstone

of treatment for patients with rheumatoid arthritis. The use of these drugs

during the perioperative period has caused debate amongst rheumatologists

and surgeons. Concerns focus on their potential to increase the risk of

infection by affecting the immune response. Rheumatoid patients are at

increased risk of infection,1 and this is of concern after surgery.2

Orthopaedic surgery in rheumatoid patients is common,3 and while it may seem

prudent to stop DMARD treatment before surgery, this may result in flare up

of disease activity. The resultant loss of mobility would adversely affect

outcome, particularly after orthopaedic procedures, where mobilisation is

crucial for effective rehabilitation.2,4

Early reports suggested that methotrexate should be stopped before

rheumatoid surgery, as it was claimed to increase infection rates. Studies

have since shown that this is not the case and methotrexate should be

continued throughout the surgical period (table 1). The effect of other

DMARDs during surgery has been less well documented. Grennan et al, using

logistic regression analysis, showed that penicillamine, indometacin,

cyclosporin, antimalarial drugs, and corticosteroids increased postoperative

complications in rheumatoid patients.4 However, they concluded that the

clinical significance of these findings was uncertain as their study had not

been designed to look at the effects of these drugs on postoperative

complications. Recently, we have shown that neither methotrexate nor

steroids, when used alone or in combination, affect the postoperative

infection rate, and we recommend that these drugs should not be stopped

before elective rheumatoid hand surgery.2

Increasing numbers of rheumatoid patients are being treated with tumour

necrosis factor (TNF) inhibitors. TNF has a pivotal role in host resistance

and as a mediator of local inflammation, although etanercept does not appear

to alter global immune function,5 and infliximab treatment restored antigen

and mitogen induced lymphocyte proliferation in vitro.6 There are no clear

guidelines on the use of cytokine inhibitors during the perioperative period

and data on surgical complications in these patients are scarce. Guidelines

for the use of infliximab in Crohn's disease state that routine use of

anti-TNF cannot be recommended before surgery.7 However, the authors concede

that no formal trial has been undertaken and, based on the opinion or

experiences of an expert committee, surgery during and after infliximab

treatment appeared to be safe.7

Despite the fact that serious infection rates in clinical trials were no

higher in those rheumatoid patients taking TNF inhibitors than in those

receiving placebo, concerns remain about infection.8 With the lack of data

on the use of anti-TNF and surgery, most clinicians would advise a cautious

approach. The UK distributors of infliximab recommend that surgery be

deferred for 2-4 weeks after the last infusion and close postoperative

surveillance maintained, although surgery soon after administration of the

drug is not absolutely contraindicated. After surgery, patients should be

monitored closely as the long term effects of TNF inhibition may mask signs

of infection.9 Anti-TNF treatment could be restarted 3 weeks after surgery,

when the incisions should have healed.

Like anti-TNF, trials of the interleukin 1 receptor antagonist anakinra

showed that the infection rate was similar to that in patients receiving

placebo.10 Currently there are no specific data on the use of anakinra

perioperatively. Therefore, a cautious approach is again warranted, with

close postoperative surveillance.

Increasing use of cytokine inhibitors means that more patients receiving

these drugs are likely to require surgical procedures in the future, despite

improved disease control. Because of the small number of these patients

currently being treated by individual surgeons, pooling of data and

multicentre trials are essential for the production of meaningful

guidelines.

ACKNOWLEDGEMENTS

A Jain was funded by an Arthritis Research Campaign Clinical Research

Fellowship. The sponsor had no role in writing of the report.

FOOTNOTES

CONFLICT OF INTEREST STATEMENT

The Kennedy Institute received a research grant and payment (according to

the number of patients) for clinical trials of an anti-TNF antibody from

Centocor Inc, Malvern, Pennsylvania, USA. Professor Maini has acted as a

consultant.

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