As guidelines recommend, doctors appear to be stopping anti-TNF medications before surgery, but may be doing so far sooner than is necessary, according to a new study by researchers at Hospital for Special Surgery. These medications are used to treat a variety of inflammatory diseases, including rheumatoid arthritis, and better timing of withdrawal prior to surgery might minimize the risk of disease flares.
"We need to do more studies to see if more pharmacologically-based timing of when you hold these medications -- maybe tie it more to their half life -- might potentially decrease rates of postoperative flares," said Lisa Mandl, M.D. MPH, a rheumatologist at HSS. She is principal investigator of the study that will be presented on Nov. 8 at the American College of Rheumatology's annual meeting.
Anti-tumor necrosis factor (anti-TNF) medications are increasingly being used in patients with rheumatoid arthritis (RA) due to their effectiveness. Because these medications suppress the immune system, guidelines recommend stopping anti-TNF therapy before any type of surgery. Few studies, however, have examined what happens in actual practice or the effect of stopping medications on patients.
To investigate the issue in knee replacement surgery, a common surgery in RA patients, researchers utilized data from the HSS Total Joint Replacement Registry. This prospective registry started in 2007 includes, among other things, data on all patients who seek care at HSS for a total knee replacement (TKR). "Other institutions may have similar registries, but we do such a high volume of surgeries that other people might take decades to get what we do in a few years. We have large numbers and it is a contemporary registry, so it's not 10,000 patients over the last 20 years. It is 20,000 over the last five years," Dr. Mandl said. The database gives doctors a snapshot of what is happening in present day practice.
Through a retrospective chart review of patients in this registry who had undergone a TKR between June 2007 and May 2010, HSS researchers identified 194 patients with RA. Cases were identified by medical billing code (ICD-9) or self-report, and then confirmed by chart review; 86 (41.4%) used anti-TNFs, predominantly etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). When investigators checked the charts, they found that 86 percent of them documented that anti-TNFs should be held and 74 percent identified a specific stop time.
While the recommended stop time should have been based on the half-life of the medications (how long the medicines stay in the body), the data did not show this to be the case. For individuals on etanercept, which has a half-life of 3 to 5.5 days, the average stop time was 2.4 weeks prior to surgery. For adalimumab, which has a half-life of 1.4 to 2.9 weeks, the average stop time was 4.6 weeks. For infliximab, which has a half-life of 1 to 1.7 weeks, the average stop time was 4.9 weeks.
All patients in the HSS Total Joint Replacement Registry receive a six-month adverse events survey and, for this study, an additional survey was sent to patients if they had not yet replied to maximize response rates. Study participants also received an RA specific questionnaire that collected information such as how long they had been impacted by the disease and whether they had any arthritis flares after surgery.
Investigators analyzed self-reported flares within one month of surgery as well as six-month adverse events, including surgical site infection, pulmonary embolism, deep venous thrombosis, re-operations, and infections such as pneumonia. They found no statistically significant difference in adverse events between patients who received anti-TNFs and those who did not. The self-reported RA flare rate was higher in the anti-TNF groups (22.4% vs. 16.9%), although this difference was not statistically significant (P=0.47).
"At least in this relatively small sample, it doesn't look like there are any increases in infections or blood clots or other problems that go along with these anti-TNFs, which is comforting for patients who are on these drugs who are going in for surgery," Dr. Mandl said.
She said that more work should be done to evaluate if the half-lives of the medications should be considered more carefully when determining when to pull the drugs from patients before a procedure. "Maybe we won't have to stop patients so early," Dr. Mandl said. "We need to think a little bit more about how we hold them to optimize how patients do after surgery."
Other HSS investigators involved in the study are Beverly Johnson, M.D., Susan Goodman, M.D., and Michael Alexiades, M.D.
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