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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 α (TNFα) inhibitors. TNFα 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-TNFα 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 TNFα inhibitors than in those receiving placebo, concerns remain about infection.8 With the lack of data on the use of anti-TNFα 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 TNFα inhibition may mask signs of infection.9 Anti-TNFα treatment could be restarted 3 weeks after surgery, when the incisions should have healed.
Like anti-TNFα, 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.
A Jain was funded by an Arthritis Research Campaign Clinical Research Fellowship. The sponsor had no role in writing of the report.
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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