RESEARCH - TNF inhibitors raise risk of postop infections in RA patients

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TNF inhibitors raise risk of postop infections in RA patients

Rheumawire

April 18, 2006

Janis

Baltimore, MD - TNF-inhibitor therapy raises the risk of early infectious

complications following orthopedic surgery in patients with rheumatoid

arthritis (RA), and data suggest that TNF inhibitors should be discontinued

for some period before surgery, Dr Jon T Giles (s Hopkins University

School of Medicine, Baltimore, MD) and colleagues report in the April 15,

2006 issue of Arthritis Care & Research [1].

" We discontinue etanercept two weeks prior to surgery, infliximab eight

weeks prior to surgery, and adalimumab four weeks prior to surgery. We

restart all three of them two weeks after surgery. We do this for all

patients, since our data showed that the risk was significant even when

adjusting for confounding factors that might also influence infection risk,

such as prednisone use, diabetes, or RA duration, " Giles told rheumawire.

First study to link TNF inhibitors to infection after joint surgery

Giles reviewed medical records in his institution's RA database for all

patients with RA who had attended the s Hopkins Arthritis Clinic at

least once between January 1, 1999 (the approximate date of the commercial

introduction of TNF inhibitors) and March 15, 2004 who had at least one

orthopedic procedure. The analysis included 217 patients who had required

hospitalization, any surgical procedure, or treatment of any infection

requiring intravenous (IV) antibiotics. Of these, 91 patients underwent at

least one orthopedic surgical procedure, and 10 (11%) of those 91 developed

a serious postoperative orthopedic infection.

The investigators found that those who developed a serious infection were

significantly more likely to have been treated with a TNF inhibitor

(p=0.041) and significantly less likely to have undergone large-joint

primary arthroplasty (p=0.006). " [T]o our knowledge, this is the first

systematic investigation linking TNF-inhibitor therapy in RA to an

infectious orthopedic surgical outcome, " the authors write.

" Prior to this study, we had conducted a small retrospective review of 30 RA

patients undergoing hip or knee arthroplasty by one orthopedist at our

hospital. From this small sample, there were no infections at all, [in

TNF-inhibitor-treated patients] or otherwise. Because of that, we decided to

systematically review all of the patients within the s Hopkins Arthritis

Center database to have a more complete picture, with the preliminary hunch

that we probably would not see an association. In that respect, we were a

little surprised. Of course, that demonstrates the value of systematic

assessment over study designs that are essentially descriptions of selected

cases, particularly when the event of interest is relatively uncommon, "

Giles said.

Giles also noted that another observation that initially seemed alarming was

the actual rate of serious postoperative infection within the cohort (11%),

which is higher than would be expected in non-RA subjects undergoing similar

procedures. " However, it is not at all inconsistent with other published

reports in RA patients. We included only patients undergoing certain types

of ortho procedures (involving dissection into the joint space or bone), as

other types of procedures that RA patients might have (ie, tendon

procedures) would not necessarily carry the same biologic risk, considering

the known mechanisms by which TNF inhibition may promote a favorable

environment for postoperative infection, " he said.

The investigators write that their data suggest that patients should abstain

from TNF inhibitors before orthopedic surgery but that this needs

confirmation in larger prospective studies. They also point up the need for

development of clinical practice guidelines for the perioperative

prescription of TNF inhibitors.

" The biggest unknown is what period of discontinuation provides improved

safety, " Giles said. " The elimination half-lives of these agents are

essentially unknown, so it is difficult to empirically decide an interval.

We have formulated some intervals that we use within our center based on the

administration half-lives of the drugs-but these have yet to be

systematically evaluated. An obvious consideration is that one does not want

to have a flare of RA disease activity in the perioperative period, which

might compromise rehabilitation and could also increase the risk of

postoperative infection. "

Source

1. Giles JT, Bartlett SJ, Gelber AC, et al. Tumor necrosis

factor inhibitor therapy and risk of serious postoperative orthopedic

infection in rheumatoid arthritis. Arthritis Rheum 2006; 55:333-337.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org