Many patients with rheumatoid arthritis (RA) will at some point undergo orthopedic surgery, and since most of these patients take disease modifying drugs (DMARDs), it's important to optimally manage their medications before undergoing such surgery.
The dilemma, according to a new review, is whether to continue potent DMARDs and risk infection or withhold these therapies, which may cause disease flares.
The paper, written by , associate professor of clinical medicine at Weill Cornell Medical College in New York City, reviews current, sometimes limited evidence surrounding perioperative medication management for RA patients and discusses related challenges.
Action Points
- Note that this review of the literature suggests that many DMARDs can be safely continued perioperatively, provided that close monitoring for infection is undertaken.
- Be aware that adequate trials of treatment strategies in this population are lacking.
The paper was published in Seminars in Arthritis & Rheumatism.
About 58% of RA patients will undergo orthopedic surgery over the course of their illness. Over 80% of such patients take traditional and biologic DMARDs at the time of their orthopedic surgery.
Stopping these drugs can raise risks for post perative disease flare. A flare, typically accompanied by pain, swelling, and fatigue, might jeopardize the ability of a patient to comply with a rehabilitation program in the post perative period. Also, active RA increases the risk for infection, further complicating decisions regarding medication.
On the other hand, continuing therapy also carries a risk for infection,which is particularly high among the approximately 65% of RA patients taking corticosteroids (and an even higher percentage among more severely affected patients). Virtually 100% of such patients treated for 3 years will develop an infection.
Yet before an operation, RA patients frequently discontinue their disease modifying medications and increase their daily dose of corticosteroids to cover RA disease activity and flares.
The data, although pertaining to a small number of patients, suggest "that patients may be exposed to far higher corticosteroid doses than are necessary with the potential of increasing infection risk," wrote Goodman.
Given the "limited but reassuring" data on perioperative infection associated with traditional DMARDs like hydroxychloroquine, azathioprine, or sulfasalazine, most clinicians should be comfortable continuing these agents at the time of surgery although attention to renal function is important to prevent inadvertent drug accumulation, said Goodman.
Clinicians should also feel comfortable continuing methotrexate, which is the best studied DMARD in the perioperative period. One study of 388 RA patients undergoing orthopedic surgery found fewer complications in patients continuing on this therapy compared with those randomized to withhold it.
Although information on perioperative use of leflunomide is conflicting, "it is reasonable to discontinue this drug for 1 week prior to surgery to permit the drug levels to decrease, given its recognized overall infection risk," wrote Goodman.
"While the half-life of the drug is 14 to 18 days, there is evidence that toxicity is dose dependent, so this compromise approach permits a decrease in drug levels without extreme withdrawal measures until definitive evidence provides more conclusive guidance."
Increased infection is a well-recognized risk of anti-tumor necrosis factor alpha(anti-TNF alpha) therapy and the presence of an orthopedic implant significantly increases this risk. In most cases, withholding anti-TNF alpha therapy for 1.5 times the dosing interval appears reasonable, said Goodman.
While there is no direct information on surgical site infection with tocilizumab, a study comparing 22 tocilizumab-treated patients with 22 conventional DMARD treated patients found a significant difference in temperature rise and increase in C-reactive protein. The possible masking of clinical signs of infection suggests increased vigilance is needed in patients treated with this drug, said Goodman.
There's little published information on perioperative infection associated with abatacept, but given its half-life, it should be withheld for 2 to 3 weeks prior to surgery, according to Goodman.
There is also no related published data in patients treated with tofacitinib, although an increase in overall infection has been described. With a half-life of 3 hours, withholding this drug for 2 days should be protective, said Goodman.
Information from the prospective (AIR) indicates that the risk of perioperative infection with this drug isn't linked to the interval between drug infusion and surgery although patients undergoing spine surgery appear to be at higher risk of complications. Determining immunoglobulin levels may be considered in high risk patients, said Goodman.
"More work is clearly needed to clarify start and stop dates, as well as the role of other factors such as disease activity and postoperative flare, corticosteroid use, smoking, and diabetes," she concluded.
Disclosures
Goodman has no relevant conflicts of interest.
Primary Source
Seminars in Arthritis & Rheumatism
Goodman S "Rheumatoid arthritis: Perioperative management of biologics and DMARDs" Seminars Arth Rheum 2015; DOI: 10.1016/j.semarthrit.2015.01.008.