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Background: In preparation for surgery, patients being treated with disease-modifying antirheumatic drugs (DMARDs) are recommended to either continue or withhold therapy perioperatively. Some of these drugs have known effects against bone healing, hence the importance of adequately managing them before and after surgery. Objective: We aim to assess the current evidence for managing conventional synthetic and/or biologic DMARDs in the perioperative period for elective spine surgery. Methods: A systematic review of four databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included manuscripts were methodically scrutinized for quality, postoperative infections, wound healing characteristics, bone fusion rates, and clinical outcomes. Results: Six studies were identified describing the management of conventional synthetic and/or biologic DMARDs. There were 294 DMARD-treated patients described undergoing various spine surgeries such as craniovertebral junction fusions. Three of the studies involved exclusive continuation of DMARDs in the perioperative window; one study involved exclusive discontinuation of DMARDs in the perioperative window; and two studies involved continuation or discontinuation of DMARDs perioperatively. Of patients that continued DMARDs in the perioperative period, 13/50 patients (26.0%) had postoperative surgical site infections or wound dehiscence, 2/19 patients (10.5%) had delayed wound healing, and 32/213 patients (15.0%) had secondary revision surgeries. A fusion rate of 14/19 (73.6%) was described in only one study for patients continuing DMARDs perioperatively. Conclusions: The available published data may suggest a higher risk of wound healing concerns and lower than average bone fusion, although this may be under-reported given the current state of the literature.