Infection risk after surgery in people using medications for inflammatory bowel disease

Background

More than 1.2 million individuals in North America are affected by inflammatory bowel disease (IBD). IBD includes Crohn's disease and ulcerative colitis. IBD is a condition that involves inflammation in the large or small intestine(s) or both, resulting in symptoms such as diarrhea and abdominal pain. A wide variety of medications are available to treat IBD. Many of the medications used to treat IBD suppress the immune system. As a result, use of these medications may increase the risk of infection. This potential increased risk of infection is particularly concerning in people undergoing surgery.

Review question

This systematic review examines the combined data from 68 published studies to determine whether people using IBD medications around the time of surgery had more infections compared to those not using the same medications.

Study characteristics

This review is current up to 29 October 2019. It includes 68 studies of people with a diagnosis of IBD who underwent surgery. The total number of people taking part in these studies is unknown because some studies did not report the number of people included. Most participants were 18 years or older and included both men and women. We examined five IBD medication groups within our review: aminosalicylates (5-ASA), corticosteroids, immunomodulators, anti-TNF medications and anti-integrin medications. Infections were tracked for up to 30 days after surgery.

Key results

Analyses of this large set of data revealed that infection risk around the time of surgery varied, depending on which type of IBD medication the participants were using. Those being treated with corticosteroids or anti-TNF agents seemed to have more infections after surgery, while those on aminosalicylates, immunomodulators or anti-integrin agents did not seem to have more infections after surgery. These findings should be considered with caution, as our review included studies which were of limited quality, and we were therefore not able to draw any firm conclusions.

These findings could help doctors to choose which medications to use in people with IBD before surgery. Decisions should be tailored to each person's unique health needs. In addition, our review suggests the need to monitor carefully for infections after surgery in people who are on certain types of IBD medications.

Limitations

One limitation of our review is its dependence on data from a wide range of published studies, with various approaches and quality control standards. Most studies that we examined were of very low certainty in their conclusions. This review illustrates the need for future high-quality research examining the impact on infection risk after surgery of medications used to treat IBD.

Authors' conclusions: 

The evidence for corticosteroids, 5-ASA, immunomodulators, anti-TNF medications and anti-integrin medications was of low or very low certainty. The impact of these medications on postoperative infectious complications is uncertain and we can draw no firm conclusions about their safety in the perioperative period. Decisions on preoperative IBD medications should be tailored to each person’s unique circumstances. Future studies should focus on controlling for potential confounding factors to generate higher-quality evidence.

Read the full abstract...
Background: 

Medications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk.

Objectives: 

To assess the impact of perioperative IBD medications on the risk of postoperative infections within 30 days of surgery.

Search strategy: 

We searched the Cochrane IBD Group's Specialized Register (29 October 2019), MEDLINE (January 1966 to October 2019), Embase (January 1985 to October 2019), the Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception up to October 2019, and reference lists of articles.

Selection criteria: 

Randomized controlled trials, quasi-randomized controlled trials, non-randomized controlled trials, prospective cohort studies, retrospective cohort studies, case-control studies and cross-sectional studies comparing participants treated with an IBD medication preoperatively or within 30 days postoperatively to those who were not taking that medication (either another active medication, placebo, or no treatment). We included published study reports and abstracts.

Data collection and analysis: 

Two review authors independently screened titles and abstracts and extracted data. The primary outcome was postoperative infection within 30 days of surgery. Secondary outcomes included incisional infections and wound dehiscence, intra-abdominal infectious complications and extra-abdominal infections. Three review authors assessed risks of bias using the Newcastle-Ottawa Scale. We contacted authors for additional information when data were missing. For the primary and secondary outcomes, we calculated odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) using the generic inverse variance method. When applicable, we analyzed adjusted and unadjusted data separately. We evaluated the certainty of the evidence using GRADE.

Main results: 

We included 68 observational cohort studies (total number of participants unknown because some studies did not report the number of participants). Of these, 48 studies reported including participants with Crohn’s disease, 36 reported including participants with ulcerative colitis and five reported including participants with indeterminate colitis. All 42 studies that reported urgency of surgery included elective surgeries, with 31 (74%) of those also including emergency surgeries. Twenty-four studies had low risk of bias while the rest had very high risk.

Based on pooling of adjusted data, we calculated ORs for postoperative total infection rates in participants who received corticosteroids (OR 1.70, 95% CI 1.38 to 2.09; low-certainty evidence), immunomodulators (OR 1.29, 95% CI 0.95 to 1.76; low-certainty evidence), anti-TNF agents (OR 1.60, 95% CI 1.20 to 2.13; very low-certainty evidence) and anti-integrin agents (OR 1.04, 95% CI 0.79 to 1.36; low-certainty evidence). We pooled unadjusted data to assess postoperative total infection rates for the use of aminosalicylates (5-ASA) (OR 0.76, 95% CI 0.51 to 1.14; very low-certainty evidence).

One secondary outcome examined was wound-related complications in participants using: corticosteroids (OR 1.41, 95% CI 0.72 to 2.74; very low-certainty evidence), immunomodulators (OR 1.35, 95% CI 0.96 to 1.89; very low-certainty evidence), anti-TNF agents (OR 1.18, 95% CI 0.83 to 1.68; very low-certainty evidence) and anti-integrin agents (OR 1.64, 95% CI 0.77 to 3.50; very low-certainty evidence) compared to controls.

Another secondary outcome examined the odds of postoperative intra-abdominal infections in participants using: corticosteroids (OR 1.53, 95% CI 1.28 to 1.84; very low-certainty evidence), 5-ASA (OR 0.77, 95% CI 0.45 to 1.33; very low-certainty evidence), immunomodulators (OR 0.86, 95% CI 0.66 to 1.12; very low-certainty evidence), anti-TNF agents (OR 1.38, 95% CI 1.04 to 1.82; very low-certainty evidence) and anti-integrin agents (OR 0.40, 95% CI 0.14 to 1.20; very low-certainty evidence) compared to controls.

Lastly we checked the odds for extra-abdominal infections in participants using: corticosteroids (OR 1.23, 95% CI 0.97 to 1.55; very low-certainty evidence), immunomodulators (OR 1.17, 95% CI 0.80 to 1.71; very low-certainty evidence), anti-TNF agents (OR 1.34, 95% CI 0.96 to 1.87; very low-certainty evidence) and anti-integrin agents (OR 1.15, 95% CI 0.43 to 3.08; very low-certainty evidence) compared to controls.