Table 4. Peri-operative infections, data from three observational studies.

	No. of patients (TNF/ Comparator)	Baseline disease characteristics (Disease duration, HAQ or DAS scores)	Definition of infections	At Risk Period	Duration of follow up	Biologic Arm	Comparator Arm	Reported Incidence	Difference b/n anti-TNF agents
Kawakami et al 2010 [42] Case control study	RA, with joint arthroplasties 64/64	Duration: 10.6 yrs vs. 13.4 yrs	Per CDC guidelines *	Undefined	NA	Infliximab Etanercept	Non biologic DMARDs	SSI: 12.5% vs. 2% . OR 21.8 (p = 0.016)	“Flares” (Arthralgias ) reported in TNF gp only: INF vs. ETA: 2 vs. 9; p=0.02
Den Broeder 2007 [43]a	RA 196/1023	Duration: 16- 17 yrs vs. 17 yrs	CDC criteria and/ or antibiotic use	Perioperative	1 yr	Etanercept, Adalimumab, Infliximab	Non biologic DMARDs	Infection rates: No TNF use 4.0% peri-op TNF use, discontinuation :5.8% TNF use, continuation peri-op: 8.7% Continuation vs.. Discontinuation: Infection OR (CI) 1.5 (0.43-5.2)	NA
RATIO Gilson et al 2010 [44]b Case control study	Rheumatic diseases pts treated w/ TNF inhibitors and joint arthroplasties with and without SSI N=20/40	Duration: 20.4 yrs vs. 20.3 yrs	Reported by physicians and validated by investigators, 19/20 had microbial data	On TNF or < 1 yr since TNF withdrawal	At least for the duration of antibiotic therapy, up to 1 yr in some cases	Etanercept, Adalimumab, Infliximab	Etanercept, Adalimumab, Infliximab	Risk factor for TJA infection: steroid intake OR (CI): 5.0 (1.1 21.6) per 5 mg/day increase, Previously infected joint within the past yr: OR (CI): 88.3 (1.1 7071)	NA

^*CDC guidelines for SSI: diagnosis of superficial or deep incisional SSI by operators and IV or oral antibiotics in all such cases

^aRisk factors for SSI: Elbow surgery OR (CI) : 4.1 (1.6-10.1), foot/ ankle surgery 3.2 (1.6-6.5), prior skin or wound infection 13.8 (5.2-36.7); decreased risk: Duration of surgery 0.42 (0.23-0.78); SSZ use: 0.21 (0.05-0.89)

^bMSSA was the most common organism, no OIs observed, however numbers small