Surgical Infection Rate May Be Higher with Arthritis Drugs

Certain drugs can boost post-surgery infection risk in patients with inflammatory arthritis.


People with inflammatory forms of arthritis, such as rheumatoid arthritis, who take more than one traditional disease-modifying antirheumatic drug (DMARD), or a type of biologic drug known as a TNF inhibitor, have an increased risk of infection following orthopaedic surgery, according to a study published in Arthritis Care & Research in December 2013. Several studies have looked at which drugs might elevate the risk and by how much with mixed results.

This study “is one of the best out there regarding this topic,” says Tim Bongartz, MD, associate professor of rheumatology at Mayo Clinic in Rochester, Minn. Dr. Bongartz was not involved in the study.

Based on their results, senior study author Inès A. Kramers-de Quervain, MD, of the department of rheumatology at the Schulthess Clinic in Zurich, Switzerland, suggests “it may be advisable to consider stopping TNF inhibitors more than one administration interval before surgery, since the risk of postoperative infection appears to be higher if the operation occurs within this period.” An administration interval is the length of time between one injection and the next.

The researchers looked at 50,359 orthopaedic surgery cases performed between 2000 and 2008. They compared infections at the surgery site in patients with inflammatory arthritis with outcomes in patients who had a degenerative disorder or had suffered a physical trauma. They also broke down the results based on which drug or drugs the arthritis patients were taking, the timing of the last dose, and what type of surgery they had.

The study considered several classes of drugs, individually and in combination: traditional DMARDs including methotrexate (Rheumatrex, Trexall), leflunomide (Arava), sulfasalazine (Azulfidine, Sulfazine), hydroxychloroquine (Plaquenil), azathioprine (Azasan, Imuran), cyclosporine (Neoral, Gengraf) and gold (Aurofin); TNF inhibitors, including etanercept (Enbrel), adalimumab (Humira) and infliximab (Remicade); other biologics, including rituximab (Rituxan) and abatacept (Orencia); and corticosteroids.

Arthritis patients who were not taking a TNF inhibitor and were taking no DMARDS or one DMARD had only a slightly higher (not statistically significant) infection rate compared with those who didn’t have arthritis. But in people taking multiple DMARDs or a TNF inhibitor, the risk of infection was about 2.5 times higher than that of the non-arthritis group. The risk was even greater – 7 times higher – if the last dose of TNF inhibitor was given less than one administration interval prior to surgery. In the arthritis group, elbow and foot surgery had the highest infection rates. 

“The increased infection risk in individuals on TNF-alpha inhibitors was expected and our study confirmed the suspicion that the risk is significantly elevated when surgery is performed during the influence of these drugs,” says Dr. Kramers-de Quervain. “Rather surprising was the finding of the increased infection risk in individuals treated with more than one conventional DMARD compared to monotherapy [treatment with one DMARD alone].” Traditional, DMARDs are generally thought to be safe to continue prior to surgery.

But Dr. Bongartz suggests the increase in infection risk found with the use of multiple DMARDs “may be a sign of more severe disease with more difficult surgeries” and doesn’t necessarily indicate that the medications themselves increase a patient’s susceptibility to infection.

The results of this study contradict those of a study presented at the American College of Rheumatology’s annual meeting in October 2013, in which researchers from Baylor College of Medicine analyzed 6,548 Veterans’ Affairs RA patients between 1 October 1999 and 30 September 2009. They found that people taking conventional DMARDs and/or biologics (types of drugs that include TNF inhibitors and other medications) did not have an increased risk of infection after orthopaedic surgery. That study, did not distinguish among different types of RA medications or different types of surgeries, making it difficult to draw broad conclusions.

Patients who are considering stopping their arthritis medication prior to scheduled surgery must carefully weigh the benefits against the risk of a disease flare. “The decision … is highly complex and should involve the patient, rheumatologist and orthopaedic surgeons,” says Dr. Bongartz.

“Several factors will be of importance, such as the type of rheumatic disease, the extent of the disease, current disease control, possible risk of a disease flare, possible consequences of a flare – which can be much more serious in a patient with extra-articular [outside the joint] manifestations such as somebody with vital organ involvement – type of surgery, history of previous infections, et cetera,” says Dr. Bongartz.

The study authors note, “when postoperative infection occurred, the patient had to undergo several subsequent surgeries, sometimes more than five, and spend a long time in the hospital, particularly with infections at the site of an arthroplasty [joint repair or replacement]. This shows that even a small decrease in the risk of postoperative infection would be of great benefit to the patient and reduce the associated costs of treatment.”