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Foot Ankle Int. 2004 May;25(5):331-5.

Infectious and healing complications after elective orthopaedic foot and ankle surgery during tumor necrosis factor-alpha inhibition therapy.

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Department of Orthopaedic Surgery, Marshfield Clinic, WI 54449, USA.



Biologic response modifiers are assuming a larger role in the management of patients with rheumatoid arthritis. The tumor necrosis factor-alpha (TNF-alpha) inhibitors etanercept and infliximab improve patient symptoms and function. However, these agents have been associated with a risk for healing and infectious complications due to systemic blockade of TNF-alpha, a ubiquitous mediator required in the normal inflammatory response in tissue healing and infection surveillance. This study analyzed the risk of healing/infectious complications in patients undergoing elective foot and ankle surgery while being treated with TNF-alpha inhibitors etanercept and infliximab.


Patients with rheumatoid arthritis undergoing elective foot and ankle surgery over a 12-month period were prospectively followed for the development of complications in the postoperative period. All patients continued their antirheumatic medication schedule unaltered in the perioperative period. Data collected included sex, age, all medications used to treat rheumatoid arthritis, smoking history, and number of orthopaedic foot and ankle procedures performed. Patients were then stratified into two groups based on the use of immunomodulation via TNF-alpha inhibition (group 1) versus patients who did not receive TNF-alpha inhibition therapy (group 2). Groups 1 and 2 were followed and compared for the development of infectious/healing complications.


Thirty-one patients were enrolled in the study. Group 1 (n = 16) and group 2 (n = 15) patients were comparable for sex distribution, number of orthopaedic procedures performed, and use of steroids, methotrexate, leflunamide, and nonsteroidal anti-inflammatory drugs. Group 1 contained six times the number of smokers in group 2. At mean follow-up of 10.6 months (group 1) and 9.7 months (group 2), healing or infectious complications were similar in both groups. However, when total complications (healing + infection) were analyzed, group 1 (TNF-alpha inhibition, "higher risk") patients demonstrated a lower complication rate (p =.033).


The data suggest that in patients with rheumatoid arthritis undergoing elective foot and ankle surgery, the use of TNF-alpha inhibition agents may be safely undertaken in the perioperative period without increasing the risk of healing or infectious complications.

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