Pre-operative withholding of infliximab and the risk of infections after major surgery in patients with rheumatoid arthritis

Michael M Ward; Abhijit Dasgupta

doi:10.1093/rheumatology/keaa291

. 2020 Jul 25;59(12):3917–3926. doi: 10.1093/rheumatology/keaa291

Pre-operative withholding of infliximab and the risk of infections after major surgery in patients with rheumatoid arthritis

Michael M Ward ^1,^✉, Abhijit Dasgupta ¹

PMCID: PMC7733718 PMID: 32710102

Abstract

Objectives

Withholding TNF inhibitors (TNFI) before surgery has been recommended due to concern for post-operative infection. We examined the risks of post-operative infections and mortality in patients with RA in relation to the pre-operative timing of infliximab infusion.

Methods

In this population-based retrospective cohort study, we used US Medicare claims data from 2007 to 2015 to identify patients with RA who underwent coronary artery bypass grafting (CABG), aortic or vascular surgery, or bowel resection, and who were treated with infliximab in the 90 days prior to surgery. We examined associations between the timing of infusion and infections and mortality in the 30 days after surgery. We adjusted for the predicted probability of post-operative infection or death, demographic characteristics, use of MTX, post-operative blood transfusion and hospital volume.

Results

We studied 712 patients with CABG, 244 patients with vascular surgery and 862 patients with bowel resections. Post-operative pneumonia occurred in 7.4–11.9%, urinary tract infection in 9.0–15.2%, surgical site infection in 3.2–18.9%, sepsis in 4.2–9.6% and death in 3.5–7.0% among surgery cohorts. There was no association between the time from last infliximab dose to surgery and the risk of post-operative infection or mortality in any surgical cohort. No subgroups were identified that had an increased risk of infection with more proximate use of infliximab.

Conclusion

Among elderly patients with RA, risks of infection and mortality after major surgery were not related to the pre-operative timing of infliximab infusion.

Keywords: tumour necrosis factor inhibitor, infliximab, post-operative infection, rheumatoid arthritis

Rheumatology key messages

In rheumatoid arthritis, post-operative infections were not related to pre-operative timing of infliximab infusions.
Patients undergoing bowel resection, vascular surgery and coronary artery bypass surgery had similar results.
No patient subgroups had increased risk of post-operative infection with more recent infusions.

Introduction

TNF inhibitors (TNFI) are highly effective medications for the treatment of RA and several other immune-mediated conditions. In 2006–2014, 16–22% of patients with RA in the USA were treated with TNFI [1, 2]. A major concern with treatment is increased susceptibility to infection. In clinical trials, the risk of serious infections was up to 50% higher among patients treated with TNFI than among controls [3]. However, similar infection risks have not always been reported in observational studies [4, 5]. Risk of infection is higher among older patients, and varies among TNFI, with the highest risk of serious infection associated with infliximab [3, 5, 6]. Among elderly patients with RA treated with infliximab, the rate of hospitalized infection was 17/100 person-years, most commonly due to lower respiratory and urinary tract infections (UTI) [7].

Major surgery is a time when patients are more vulnerable to infection, raising questions about how TNFI treatment should be managed preoperatively. Temporarily withholding TNFI prior to surgery has been presumed to reduce the risk of post-operative infection, but carries a potential risk of RA flare. Professional societies have recommended withholding TNFI for one dosing interval prior to elective arthroplasty, and for 3–5 drug half-lives prior to surgeries with higher risks of infection, although the supporting evidence is limited [8, 9]. Among patients undergoing orthopaedic surgery, two small case series reported no perioperative infections regardless of whether TNFI were withheld preoperatively, and three larger studies that included non-orthopaedic procedures found no difference in either surgical site infections or serious infections between patients who either continued or withheld TNFI preoperatively [10–14]. In contrast, other studies that primarily included orthopaedic procedures reported risks of post-operative infections or complications that were >50% higher among patients who continued TNFI preoperatively [15–17]. Orthopaedic surgeons typically instruct patients to withhold TNFI preoperatively, although with considerable variability in the recommended interval [18].

Elective orthopaedic procedures have very low risks of perioperative infection. In 2013, the US Centers for Disease Control and Prevention National Healthcare Safety Network reported surgical site infections in 0.37% of knee arthroplasties, compared with 0.7% of coronary artery bypass grafting surgery (CABG), 1.8% of peripheral artery bypass surgery, and 2.78% of colon surgeries [19]. These differences in baseline risk make it difficult to generalize the findings in joint arthroplasty to surgeries with greater risks of infection. We undertook this study to examine the hypothesis that withholding TNFI preoperatively was associated with a lower risk of post-operative infection and mortality in patients with RA who were undergoing major surgery other than arthroplasty. We examined patients having CABG surgery, aortic or lower extremity arterial bypass surgery, and large or small bowel resections, to study procedures with higher baseline risks of infection. We studied patients treated with infliximab because the timing of the infusion relative to surgery was precisely known, in contrast to injectable TNFI.

Methods

Data source

We used Medicare hospitalization, outpatient and medication claims data for analysis. Medicare is the federally funded medical insurance programme that covers elderly Americans. We used data from 2006 to 2015 on beneficiaries who had full inpatient, outpatient and drug coverage during these years. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9) codes were used for diagnoses and procedures through 30 September 2015. Data access was provided by the US Centers for Medicare and Medicaid Services (CMS) by a data use agreement, and the study protocol was approved by the National Institute of Diabetes and Digestive and Kidney Diseases institutional review board, with waiver of informed consent.

Study cohorts

The three cohorts studied were patients with RA who underwent CABG, vascular surgery, or open or laparoscopic bowel resection and who were being treated with infliximab at the time of surgery. We first identified patients with RA as those with at least two outpatient visits in 2006–2015 with an ICD9 diagnosis code of 714.0 by a rheumatologist. This definition, along with prescription of a disease-modifying medication, has been reported to have a positive predictive value of 0.89 for a diagnosis of RA among Medicare beneficiaries [20]. Among these patients, we identified those who underwent one of the three types of surgery between 1 January 2007 and 30 June 2015, using the corresponding ICD9 procedure codes: CABG: 36.1 and 36.2; vascular surgery, including abdominal aortic surgery or lower extremity artery bypass: 38.44, 38.46, 38.48, 38.49, 38.18, 39.25 and 39.29; and small bowel, large bowel or rectal resection: 45.6, 45.7, 45.82, 48.5 and 48.6. We then identified those who were treated with infliximab in the 90 days prior to surgery, based on the date of the most recent infusion [Healthcare Common Procedure Coding System (HCPCS) code J1745]. The maintenance dosing interval of infliximab in RA is typically 8 weeks, and its elimination half-life is 9 days [21]. Therefore, studying patients who received infliximab in the 90 days prior to surgery would include those within and outside the recommended withholding period of ∼50 days. Because the continued use or withholding of injectable TNFI could not be ascertained in the dataset, we limited the study to patients treated with infliximab.

Outcomes

The occurrence of four types of infections (pneumonia, UTI, surgical site infections and sepsis) in the 30 days after surgery were identified by relevant ICD9 diagnosis codes in claims of the index hospitalization or any rehospitalization, or subsequent outpatient claims (see Supplementary Table S1, available at Rheumatology online). The diagnosis codes used to identify sepsis, pneumonia and UTI were those designated by Medicare to classify hospital-associated infections, while the codes used for surgical site infections were those designated by the Centers for Disease Control and Prevention National Healthcare Safety Network [22, 23]. Infections present on admission were not counted. We also examined all-cause mortality in the 30 days after surgery.

Covariates

Demographic data were abstracted from the master beneficiary files. We used data on whether the beneficiary received state-provided subsidies for medical insurance premiums as an indicator of whether the beneficiary was poor. Low socioeconomic status has been associated with increased risks of post-operative infection [24, 25]. We used medication data to identify patients treated with MTX, sulfasalazine, leflunomide, hydroxychloroquine or prednisone at the time of surgery, and those who were treated with parenteral corticosteroids in the 14 days prior to surgery.

We used the American College of Surgeons (ACS) National Surgical Quality Improvement Program Surgical Risk Calculator to adjust for the expected risk of post-operative infection [26, 27]. This calculator was developed for use in shared decision-making to provide patients with estimates of their likely post-operative outcomes. The risk estimates provided by the calculator were based on validated data on over 1.4 million surgeries in 393 US hospitals from 2009 to 2012, including CABG, vascular and bowel surgeries [26]. The calculator provides patient-specific 30-day probabilities of post-operative pneumonia, UTI, surgical site infection, sepsis and mortality, based on the specific surgical procedure [by Common Procedural Terminology (CPT) code] and 19 demographic and clinical features: age, sex, functional status, whether the surgery was performed on an emergency basis, American Society of Anesthesiologists (ASA) Physical Status class, chronic corticosteroid use, ascites, systemic sepsis in the prior 48 h, ventilator dependency, disseminated cancer, diabetes mellitus requiring insulin or oral hypoglycaemics, hypertension, congestive heart failure, dyspnoea, current smoking, severe chronic obstructive pulmonary disease, renal dialysis, acute kidney injury and body mass index. In validation studies, the predictions based on these scores were accurate, with c statistics of 0.87, 0.80, 0.81 and 0.94 for pneumonia, UTI, surgical site infection and mortality, respectively [26]. The model provides risk estimates even when information is missing on certain clinical features. Not all clinical features contribute to the estimation of risks for each outcome and each surgical procedure, and the weights associated with specific clinical features are proprietary [27]. These risk estimates provide a propensity score for the development of post-operative infection or death among the general population of patients undergoing these surgeries. We used diagnosis codes from prior inpatient and outpatient claims as inputs in the ACS Surgical Risk Calculator (Supplementary Tables S2 and S3, available at Rheumatology online).

Post-operative blood transfusion has been associated with increased risk of infection [28, 29]. Therefore, we identified patients who received transfusions in the 3 days after surgery. The frequency of post-operative infections also tends to be lower at hospitals that perform more surgical procedures [30, 31]. We tallied the number of CABGs, vascular surgeries and bowel resections performed annually at each hospital among Medicare beneficiaries.

Statistical analysis

Each surgery cohort was analysed separately. For descriptive purposes, we examined the characteristics of patients by tertile of time from pre-operative infliximab infusion to the date of surgery. A given patient could have more than one type of post-operative infection.

Time since the infliximab infusion (as a continuous variable) was the independent variable of interest in logistic regression models examining the association with each of the four infections and mortality. We implemented the models as cubic splines to allow non-linear associations with the time since infliximab infusion. Covariates in multivariable models included the ACS Surgical Risk estimate, race (white vs non-white), poor, use of MTX, post-operative transfusion and hospital volume. Age, sex, comorbidities and corticosteroid use were not included separately because these variables were incorporated in the ACS Surgical Risk estimate.

We also used classification trees to identify any patient subgroups at increased risk of infection with more recent infliximab use. A classification tree is a non-parametric recursive partitioning method that segregates patients based on their demographic and clinical characteristics into subgroups that are increasingly enriched for (or depleted of) the outcome of interest. We used the 19 individual features of the ACS Surgical Risk score, including corticosteroid use, along with race, being poor, use of MTX, post-operative transfusion and hospital volume as candidate classifiers. From among these classifiers, the programme first selects the variable that best segregates patients into subgroups with higher or lower likelihoods of infection. Each variable is then iteratively evaluated for its ability to segregate patients into subgroups with higher or lower likelihoods of infection in each daughter group. Group splits were based on improvement in the Gini coefficient, with the daughter groups set to a minimum of 30 patients.

Following CMS policies, we suppressed results when any cell contained fewer than 11 patients. We used SAS version 9.4 (SAS Institute, Cary NC, USA) for analysis.

Results

We studied 712 patients who underwent CABG, 244 patients who had vascular surgery and 862 patients with bowel resection. The most common principal diagnoses in the CABG cohort were coronary atherosclerosis (62.2%) and subendocardial infarction (13.6%). In the vascular surgery cohort, the most common principal diagnoses were lower extremity atherosclerosis (51.2%), aortic aneurysm (18.8%) and arterial thromboembolism (7.7%). The most common procedures were femoral-popliteal bypass graft other than vein (CPT 35656) in 16.4%, thromboendarterectomy of common femoral artery (CPT 35371) in 9.8% and femoral-popliteal bypass graft with vein (CPT 35556) in 7.8%. In the bowel resection cohort, the most common principal diagnoses were colonic diverticulitis (15.9%), colon cancer (15.9%) and intestinal adhesions with obstruction (8.3%). The most common procedures were enterectomy–resection of small intestine (CPT 44120) in 19.6%, partial colectomy with anastomosis (CPT 44140) in 19.1%, partial colectomy with end colostomy (CPT 44143) in 12.6%, and partial colectomy with ileocolostomy (CPT 44160) in 12.0%.

The CABG cohort included equal proportions of men and women, while women predominated in the vascular surgery and bowel resection cohorts, as expected for groups with RA (Table 1). MTX was used by 28–33% of patients across cohorts, while fewer than one-fifth were treated with corticosteroids. Median estimated risks of post-operative infections and death based on the ACS Surgical Risk Calculator were generally low, but estimates varied widely among patients.

Table 1.

Characteristics of patients undergoing coronary artery bypass graft surgery, vascular surgery or bowel resection

Characteristic	CABG	Vascular surgery	Bowel resection
Characteristic	(n = 712)	(n = 244)	(n = 862)
Age, mean (s.d.), years	72.4 (7.2)	74.2 (8.0)	74.0 (8.3)
Women, n (%)	362 (50.8)	165 (67.6)	688 (79.8)
White, n (%)	671 (94.2)	211 (86.5)	778 (90.2)
Poor, n (%)	52 (7.3)	33 (13.5)	87 (10.0)
Diabetes, n (%)	259 (36.3)	74 (30.3)	223 (25.8)
Hypertension, n (%)	551 (77.3)	210 (86.0)	651 (75.5)
Chronic obstructive pulmonary disease, n (%)	201 (28.2)	102 (41.8)	253 (29.3)
Obesity, n (%)	49 (6.9)	13 (5.3)	79 (9.1)
Current smoker, n (%)	59 (8.3)	58 (23.7)	68 (7.9)
Congestive heart failure, n (%)	198 (27.8)	31 (12.7)	62 (7.1)
ASA class, n (%)
2	64 (9.0)	47 (19.2)	218 (25.2)
3	366 (51.4)	175 (71.7)	546 (63.3)
4	276 (38.7)	18 (7.3)	41 (4.7)
Emergency hospitalization, n (%)	153 (21.4)	40 (16.3)	354 (41.0)
MTX, n (%)	203 (28.5)	82 (33.6)	243 (28.1)
Leflunomide, n (%)	28 (3.9)	—	17 (2.0)
Hydroxychloroquine, n (%)	39 (5.4)	18 (7.3)	38 (4.4)
Prednisone, n (%)	104 (14.6)	50 (20.4)	165 (19.1)
Parenteral corticosteroids, n (%)	16 (2.2)	—	24 (2.7)
Pneumonia probability, median (range)^a	3.3 (0.2–14.5)	2 (0.1–27.0)	4.2 (0.2–29.1)
Urinary tract infection probability, median (range)^a	1.7 (0.15–5)	1.55 (0.2–4.4)	2.9 (0.3–9.5)
Surgical site infection probability, median (range)^a	2 (0.4–5.1)	5.3 (0.5–13.4)	9.6 (0.4–23.9)
Sepsis probability, median (range)^a	1.5 (0–7.2)	2.1 (0–18.6)	5.25 (0–27.7)
Death probability, median (range)^a	1.5 (0–22.9)	1.7 (0–30.6)	3.1 (0–50.6)
Hospital procedure volume, median (range)	210 (10–1161)	51 (1–234)	81 (1–559)
Transfusion with 72 h, n (%)	150 (21.0)	44 (18.0)	108 (12.5)
Days since infliximab, median (range)	36 (1–90)	36 (1–90)	37 (0–90)

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Cells based on data of fewer than 11 patients are suppressed. ^aBased on the American College of Surgeons Surgical Risk Calculator. ASA: American Society of Anesthesiologists.

The median time from infliximab infusion to surgery was 36 or 37 days in each cohort (Table 1). Infliximab was administered within 2 weeks of surgery in 13.7%, 12.7% and 12.7% of patients in the CABG, vascular surgery and bowel resection cohorts, respectively. Patient characteristics, including estimated risks of infection and mortality, were similar among patients whose infliximab infusion was either recent or remote from surgery (Supplementary Tables S4–S6, available at Rheumatology online).

Pneumonia and UTI were the most common post-operative infections among patients with CABG, occurring in 10.4% and 13.6%, respectively (Table 2). In both the vascular surgery and bowel resection cohorts, surgical site infections and UTI were most common. Post-operative mortality occurred in 9.9% of patients in the bowel resection group. Results for sepsis after vascular surgery were not reported due to the small number of events. The probability of infection and death as estimated by the ACS Surgical Risk Calculator was positively associated with development of the corresponding event, with odds ratios ranging from 1.04 to 2.47 per 1% increase in the Risk Calculator prediction (Supplementary Table S7, available at Rheumatology online).

Table 2.

Post-operative infections and mortality by type of surgery

Outcome	CABG	Vascular surgery	Bowel resection
Outcome	(n = 712)	(n = 244)	(n = 862)
Pneumonia, n (%)	74 (10.4)	18 (7.4)	103 (11.9)
Urinary tract infection, n (%)	97 (13.6)	22 (9.0)	131 (15.2)
Surgical site infection, n (%)	23 (3.2)	25 (10.2)	163 (18.9)
Sepsis, n (%)	30 (4.2)^a	—	75 (9.6)^b
Death, n (%)	25 (3.5)	17 (6.9)	86 (9.9)

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Cells based on data of fewer than 11 patients are suppressed. ^aBased on 702 patients without sepsis on admission.

Based on 775 patients without sepsis on admission.

The occurrence of post-operative infections and deaths relative to the preoperative timing of infliximab infusion is shown in Fig. 1. There was no evident increase in infections or mortality among patients whose infusion was close to surgery.

Adjusted risks of post-operative infections and death in relation to the timing of infliximab infusion are shown in Fig. 2. In each cohort, there was no significant association between the recency of infliximab infusion and risk of post-operative infection or death. To determine whether a recent infliximab infusion might be associated with greater risk among patients with a higher expected probability of infection, we tested interactions between the time since infusion and the probability of infection based on the ACS Surgical Risk Calculator. None of these interactions was significant.

In the classification tree analysis of patients with CABG, acute kidney injury and sex discriminated subgroups with different risks of infection (Fig. 3). Among women without acute kidney injury, infliximab use closer to surgery was associated with a lower risk of post-operative infection. Similarly, among patients in the bowel resection cohort, emergency surgery and dyspnoea identified a high-risk subgroup, but among those without dyspnoea, infliximab use closer to surgery was associated with a lower risk of infection. No other variables were identified to be important classifiers. No subgroups were identified in the vascular surgery cohort that had higher or lower risks of infection than the overall group. Use of corticosteroids or MTX did not classify patients at increased risk of post-operative infection.

Fig. 3 — Classification tress for the risk of any post-operative infection

Percentages indicate the percentage with any post-operative infection in each group. n indicates the number in each group.

Discussion

In this population-based study, we found no association between the timing of infliximab infusion prior to surgery and the risk of post-operative infections or mortality among patients with RA undergoing CABG, vascular surgery or bowel resection. These results are similar to several studies of orthopaedic procedures, even though the surgeries we examined have higher risks of infection [10–13]. Both the types of surgery and the older age of the cohorts provide a more stringent test of whether continuation of infliximab close to surgery is associated with an increased risk of infection. We also did not identify any patient subgroups among which more proximate use of infliximab was associated with a greater risk of post-operative infections. This is important because while there may not be an association with the timing of infliximab in the overall group, risks of post-operative infections might have been elevated in smaller subgroups defined by particular clinical characteristics or co-medications.

Three prior studies reported higher rates of post-operative infection when TNFI were not withheld prior to surgery. Ruyssen-Witrand et al. reported complications (primarily infection or delayed healing) in 3 of 10 (30%) patients who continued TNFI within two drug half-lives of surgery compared with 7 of 36 patients (19%) who discontinued TNFI for at least five drug half-lives before surgery [15]. Similarly, surgical site infections occurred in 5.8% of 104 orthopaedic procedures when TNFI had been discontinued for at least four drug half-lives, compared with 8.7% of 92 procedures with more recent TNFI use [16]. In the study of Scherrer et al. surgery within one dosing interval of TNFI administration was associated with a 10-fold higher risk of infection, but only eight infections were observed among 171 procedures [17]. Given the small numbers, these associations may have been due to chance. It is important to distinguish these studies from studies that compare infection risks between patients treated with TNFI and those who are not using TNFI [32–34]. The latter studies address the fundamentally different question of TNFI as a risk factor for infection, and are influenced by confounding by indication. These studies do not inform whether withholding TNFI prior to surgery among patients on maintenance treatment affects post-operative infection risks.

The question of pre-operative withholding of TNFI has also been examined in patients with inflammatory bowel disease. In a US claims-based study of 650 patients with ulcerative colitis undergoing intestinal surgery within 90 days of TNFI use, there was no association between the timing of pre-operative TNFI and the risk of post-operative complications or readmission [35]. Two smaller studies also found no association [36, 37]. These findings support our results on bowel resections in patients with RA. In patients with Crohn’s disease, TNFI serum levels at surgery have been proposed as a more specific marker of post-operative infection risk than time since drug administration, but further studies are needed to assess the prognostic value of drug level testing [38].

The strengths of this study include the national population-based sample, examination of three types of surgery, and adjustment for propensity of infection using a validated risk score. The study is limited in that we only examined infliximab, and only examined patients with RA. We do not know if associations are similar for other TNFI or for patients with other diseases. However, since infection risks are higher with infliximab than with other TNFI, and higher in patients with RA than in those with psoriasis or spondyloarthritis [5, 39–41], our study likely had greater opportunity to detect infection risks associated with pre-operative continuation of TNFI. We did not examine other outcomes such as wound healing, or complications after 30 days. Later complications would be more difficult to attribute to pre-operative infliximab use. We used claims data rather than medical record data as inputs for the ACS Surgical Risk Calculator, which may have resulted in over- or underestimation of estimated infection probabilities in some patients. However, accuracy was likely acceptable for the purpose of risk adjustment, and the associations between the probabilities and observed infections supports the validity of these estimates. The contribution of corticosteroid use to the risk estimates was based on its use for any indication, which may include higher doses than those typically used in RA. However, only 20% of patients in this study were treated with corticosteroids. We did not analyse infliximab dose because data on patient weight were not available. Lastly, the study was observational and cannot address causation.

Risks of post-operative infections were not higher among patients who received infliximab close to surgery compared with those who received infliximab remotely, suggesting that withholding infliximab prior to major surgery may not reduce infection risks. It is important to recognize that these results reflect the average outcomes of many patients, and may not apply equally to all patients. Individualized decision-making regarding withholding of infliximab prior to elective surgery based on a patient’s estimated infection risk is warranted. Our results also suggest that infections that occur post-operatively in patients who received infliximab close to surgery should not necessarily be attributed to the use of infliximab.

Supplementary Material

keaa291_supplementary_data

Click here for additional data file.^{(30.4KB, docx)}

Acknowledgements

Data were provided by the US Centers for Medicare and Medicaid Services under a data use agreement, which prohibits public dissemination of the primary data. Qualified investigators may apply to this agency for access to the primary data.

Funding: This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (ZIA-AR-041153).

Disclosure statement: The authors have declared no conflicts of interest.

Supplementary data

Supplementary data are available at Rheumatology online.

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26. Bilimoria KY, Liu Y, Paruch JL. et al. Development and evaluation of the Universal ACS NSQIP Surgical Risk Calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surg 2013;217:833–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.ACS NSQIP. Surgical Risk Calculator. https://riskcalculator.facs.org/RiskCalculator/index.jsp (4 September 2019, date last accessed).
28. Duffy G, Neal KR.. Differences in post‐operative infection rates between patients receiving autologous and allogeneic blood transfusion: a meta‐analysis of published randomized and nonrandomized studies. Transfus Med 1996;6:325–8. [DOI] [PubMed] [Google Scholar]
29. Chang H, Hall GA, Geerts WH. et al. Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection. Vox Sang 2000;78:13–8. [DOI] [PubMed] [Google Scholar]
30. Farber BF, Kaiser DL, Wenzel RP.. Relation between surgical volume and incidence of postoperative wound infection. N Engl J Med 1981;305:200–4. [DOI] [PubMed] [Google Scholar]
31. Wu SC, Chen CC, Ng YY, Chu HF.. The relationship between surgical site infection and volume of coronary artery bypass graft surgeries: Taiwan experience. Infect Control Hosp Epidemiol 2006;27:308–11. [DOI] [PubMed] [Google Scholar]
32. Mabille C, Degboe Y, Constantin A. et al. Infectious risk associated to orthopaedic surgery for rheumatoid arthritis patients treated by anti-TNFalpha. Joint Bone Spine 2017;84:441–5. [DOI] [PubMed] [Google Scholar]
33. George MD, Baker JF, Winthrop K. et al. Risk of biologics and glucocorticoids in patients with rheumatoid arthritis undergoing arthroplasty: a cohort study. Ann Intern Med 2019;170:825–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
34. Goodman SM, Menon I, Christos PJ, Smethurst R, Bykerk VP.. Management of perioperative tumour necrosis factor α inhibitors in rheumatoid arthritis patients undergoing arthroplasty: a systematic review and meta-analysis. Rheumatology 2016;55:573–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
35. Kulaylat AS, Kulaylat AN, Schaefer EW. et al. Association of preoperative anti–tumor necrosis factor therapy with adverse postoperative outcomes in patients undergoing abdominal surgery for ulcerative colitis. JAMA Surg 2017;152:e171538. [DOI] [PMC free article] [PubMed] [Google Scholar]
36. Nørgård BM, Nielsen J, Qvist N. et al. Pre‐operative use of anti‐TNF‐α agents and the risk of post‐operative complications in patients with ulcerative colitis – a nationwide cohort study. Aliment Pharmacol Ther 2012;35:1301–9. [DOI] [PubMed] [Google Scholar]
37. Waterman M, Xu W, Dinani A. et al. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease. Gut 2013;62:387–94. [DOI] [PubMed] [Google Scholar]
38. Lau C, Dubinsky M, Melmed G. et al. The impact of preoperative serum anti-TNFα therapy levels on early postoperative outcomes in inflammatory bowel disease surgery. Ann Surg 2015;261:487–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
39. van Dartel SA, Fransen J, Kievit W. et al. Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Ann Rheum Dis 2013;72:895–900. [DOI] [PubMed] [Google Scholar]
40. Lane MA, McDonald JR, Zeringue AL. et al. TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis. Medicine 2011;90:139–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
41. Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP.. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 2013;72:517–24. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Supplementary Materials

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[keaa291-B35] 35. Kulaylat AS, Kulaylat AN, Schaefer EW. et al. Association of preoperative anti–tumor necrosis factor therapy with adverse postoperative outcomes in patients undergoing abdominal surgery for ulcerative colitis. JAMA Surg 2017;152:e171538. [DOI] [PMC free article] [PubMed] [Google Scholar]

[keaa291-B36] 36. Nørgård BM, Nielsen J, Qvist N. et al. Pre‐operative use of anti‐TNF‐α agents and the risk of post‐operative complications in patients with ulcerative colitis – a nationwide cohort study. Aliment Pharmacol Ther 2012;35:1301–9. [DOI] [PubMed] [Google Scholar]

[keaa291-B37] 37. Waterman M, Xu W, Dinani A. et al. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease. Gut 2013;62:387–94. [DOI] [PubMed] [Google Scholar]

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[keaa291-B40] 40. Lane MA, McDonald JR, Zeringue AL. et al. TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis. Medicine 2011;90:139–45. [DOI] [PMC free article] [PubMed] [Google Scholar]

[keaa291-B41] 41. Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP.. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 2013;72:517–24. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

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