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 new study published in Arthritis Care & Research in December.

It is not a new theory that drugs taken for inflammatory arthritis conditions, which in many cases work by suppressing the immune system, might increase post-surgical infections. Over the years, a host of studies has looked at which drugs might elevate the risk and by how much. The results have not been clear.

But 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 the outcomes (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.

Overall, 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.