{'fraction_non_alphanumeric': 0.019662921348314606, 'fraction_numerical': 0.009461856889414548, 'mean_word_length': 5.658464566929134, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Elucidating the Risks and Benefits of Withholding Biologics to Optimize Surgical Outcomes

The introduction of biologic therapies for the treatment of rheumatoid arthritis (RA) has resulted in a paradigm shift in the experience of RA for both patients and clinicians. These genetically engineered therapies target and disrupt specific immune system signals that cause and perpetuate the disease. Although not a cure for RA, biologic therapies can dramatically slow disease progressionbut they may also increase risk for infection. George and colleagues (1) report a retrospective cohort study that used administrative claims data (Medicare and Truven MarketScan) to compare infection risk across biologic therapies in the setting of primary or revision joint replacement surgery of the hip or knee in adults with RA. They examined the relationship between use of biologic therapies and glucocorticoids (none, 5 to 10 mg/d, and >10 mg/d) in the 90 days before surgery and hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between January 2006 and September 2015. Secondary outcomes included the risk associated with concomitant use of methotrexate. In propensity-adjusted analyses, the authors found no significant differences in risk for infection outcomes across biologic therapies. However, the number of patients receiving rituximab or tocilizumab was small, precluding confidence in the finding of lower infection risk with rituximab. Concomitant use of methotrexate was not associated with a significantly higher risk for infection, and results were similar for secondary and exploratory outcomes and in sensitivity analyses. Although this is encouraging, the authors found a significant dose-related increase in risk for 30-day hospitalized infection and PJI associated with glucocorticoid use: Risk for each outcome was almost 2-fold higher in patients receiving more than 10 mg/d than in those not receiving glucocorticoids. The 2017 guideline from the American College of Rheumatology and American Association of Hip and Knee Surgeons on perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing arthroplasty (2) recommends withholding biologic agents before surgery to reduce infection risk. The recommendations are for all biologic agents because evidence suggests a lack of variability in infection risk, which these findings support. To our knowledge, no randomized controlled clinical trials to date have examined the effect of biologic therapies on postoperative infection among patients with RA receiving hip or knee replacement. Thus, the recommendation to withhold biologic therapies perioperatively was based on indirect evidence (35). In a Dutch registry, Cordtz and colleagues (6) showed that patients with RA treated with biologic agents did not have a statistically significant increased risk for PJI (standardized hazard ratio, 1.61 [95% CI, 0.70 to 3.69]) compared with those not receiving biologic therapies (6). Unfortunately, the current study did not have a nonbiologic therapy group, nor could the authors discriminate those whose therapy was versus was not withheld. Risk for serious postoperative infection after joint replacement surgery is increased 1.5-fold in patients with RA (7). Whether biologic therapies further increase this risk remains unclear. An obvious concern about withholding biologic therapies in the perioperative period is that this may result in RA flare, necessitating an increase in glucocorticoid dosage. Given the strong relationship between glucocorticoid therapy and risk for postoperative infection found in this study and others, additional research is warranted to determine the management approach that is associated with lowest risk for serious postoperative infection. The study by George and colleagues examined infection risk after primary and revision procedures; revision arthroplasty is associated with higher risk for postoperative complications. However, most surgical procedures included in the analyses were primary (89.5%), and a sensitivity analysis excluding revisions showed similar findings. Patients with RA having hip replacement were also combined with those having knee replacement. Prior work has found that patients with RA undergoing primary knee replacement are at increased risk for postoperative infection, whereas recipients of primary hip replacement are not (8). Unfortunately, the current study did not provide a stratified analysis. Thus, whether infection risk differs for recipients of hip versus knee replacement receiving biologic therapies remains unclear. Higher annual volumes of joint replacement surgery by surgeon and hospital predict lower rates of complications, including PJI (8). In a prior study by Ravi and colleagues (9), greater surgeon experience with joint replacement in patients with RA was also associated with lower complication rates, regardless of the surgeon's overall experience with total joint arthroplasty and regardless of hospital factors, including joint replacement volume. In the current study, procedures were predominantly done in low-volume hospitals: Only 128 of 2228 hospitals (5.8%) in the Medicare database for which surgical volumes were available did more than 10 procedures annually. As a result, the reported infection rates may be higher than those seen in higher-volume hospitals. Although not addressed by the current study, surgeon and hospital experience performing joint replacement surgery in patients with RA should be considered in physician referral to optimize patient outcomes. George and colleagues aimed to determine whether risk for infection after hip or knee arthroplasty varied depending on the biologic therapy used and contextual factors, such as concomitant use of methotrexate or glucocorticoids. The study has provided convincing evidence to support lack of variability in postoperative infection risk across the available biologic therapies, with the aforementioned caveat about insufficient experience to date with rituximab and tocilizumab. The findings should also be reassuring regarding the lack of evidence for increased infection risk with methotrexatebiologic cotherapy, which almost half of the study population was receiving. However, the study does not resolve the question of whether withholding biologic therapies in the perioperative period actually reduces patients' overall risk for infection complications. Instead, it provides compelling evidence, once again, of the substantial risk for serious postoperative infections associated with glucocorticoid use. There is a critical need for research to elucidate the risks and benefits of withholding biologics to optimize patient outcomes.