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 in New York. 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 post-operative flares," said Lisa Mandl, M.D. MPH, a rheumatologist at HSS. She is principal investigator of the study that is being presented 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 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 researchers utilized data from the HSS Total Joint Replacement Registry. 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. Of these, 41.4 percent used anti-TNFs, predominantly etanercept, adalimumab, and infliximab. 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, 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.
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, although this difference was not statistically significant.
"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."