Methotrexate

▪Usually given once weekly

▪A prospective randomized trial of patients with RA undergoing elective orthopedic surgery showed fewer complications, infections, and flares in the group that continued methotrexate rather than discontinuing [2, 8]

▪A 2008 review of the eight studies of methotrexate in the orthopedic perioperative period suggested that the medication could be continued through surgery (with 6 of the 8 studies finding that methotrexate did not pose an infectious risk, while the other 2 did) [2]. No data in non-orthopedic surgery

▪Generally acceptable to continue, unless surgery is being done for a serious infection in which case it should be held [2]. Other reasons to consider stopping medication include postop infection, rising creatinine, prolonged NPO state, and patient over age 70

▪Recommend discussing with the patient’s rheumatologist

▪Leflunomide (Arava^®)

▪No clear data for the management of leflunomide, and discussion with the patient’s rheumatologist is usually warranted

▪One trial showed no difference in wound healing in orthopedic surgery patients [9]; however, a second trial showed that it did affect wound healing

▪Consider stopping in patients in whom large wounds are anticipated

▪Note that long half-life (~2 weeks) may make complete discontinuation problematic

Sulfasalazine

▪Generally acceptable to continue [10]

Azathioprine

▪May be continued for minor procedures and held for a few days for major procedures, although no clear data to suggest that this is necessary [10]

Hydroxychloroquine (Plaquenil^®)

▪Generally acceptable to continue

▪One retrospective study showed no difference in postoperative wound healing or infections [10]

TNF-alpha inhibitors—infliximab (Remicade^®), adalimumab (Humira^®), etanercept (Enbrel^®), etc.

▪Some small studies (n = 31 or fewer) have not shown a difference in orthopedic surgery, but were likely underpowered [10–12]

▪Until more studies can be done, general consensus is to hold these medications [10]

▪We recommend discussion with the patient’s rheumatologist and surgeon regarding the use of these agents in the perioperative period

▪If decision is to hold the drug (which is most likely the case for moderate to higher risk procedures), hold based on ½ life and hold at least two half-lives. Half-lives are listed below:

 Etanercept (Enbrel^®): 3.5–5.5 days

 Adalimumab (Humira^®): 10–20 days

 Infliximab (Remicade^®): 9.5 days

 Certolizumab (Cimzia^®): 14 days

 Golimumab (Simponi^®): 14 days

▪Postoperatively it is recommended to restart these agents once wound healing is complete and there is no evidence of infection; usually not earlier than 10–14 days postoperatively [10]