Postoperative Complications in Patients With IBD
Postoperative Complications in Patients With IBD
The results of this meta-analysis suggest that peri-operative treatment with anti-TNFα medications modestly increases the post-operative risk of infectious, non-infectious and total complications in patients with IBD. These conclusions are similar to those of other systematic reviews. A recent meta-analysis found a statistically significant increased risk of infectious complications (OR 1.50, 95% CI 1.08–2.08), and a nonsignificant trends towards increased non-infectious (OR 2.00, 95% CI 0.89–4.46) and overall complications (OR 1.72, 95% CI 0.93–3.19) among patients with CD undergoing abdominal surgery. Another found no increased risk of infectious (OR 1.10, 95% 0.51–2.38), non-infectious (OR 1.10, 95% CI 0.76–1.59), or total complications (OR 1.09, 95% CI 0.87–1.37) among patients with UC treated preoperatively with infliximab. Our meta-analysis is the first to include data from mixed cohorts of IBD patients. We also include more recently published manuscripts and excluded lower quality studies.
There are several limitations to the current meta-analysis. Of all eligible studies, only one assessed outcomes prospectively. Observational studies cannot control for all potential confounding factors, and this is even more challenging with retrospective designs. Only a few studies adjusted for concurrent immunosuppressive use and age. Other factors such as disease severity and the nature, indication and timing of surgery may also influence outcome and patients treated with anti-TNFα therapies are more likely to have severe disease. Notably, seven studies that reported increased risks of infectious complications also reported higher concurrent use of immunomodulators or corticosteroids in the group treated peri-operatively with infliximab. Accordingly, increases in the rate of complications may reflect differences in morbidity rather than an effect of anti-TNFα therapy.
Most studies reported both infectious and non-infectious complications. Where it was not stated clearly whether these outcomes were mutually exclusive, we contacted the authors for clarification. Waterman et al. provided detailed information about subjects who experienced more than one complication, and our analysis accounts for this. However, Appau et al. did not respond to our inquiry and we analysed their data as reported. Sensitivity analysis showed that exclusion of these data did not affect the findings of our meta-analysis. There is also variability among studies in definitions of infectious and non-infectious complications. We accepted the original authors' classification but, where this was not provided, classified outcomes based on the data provided. The classification of different outcomes is detailed in Table S1.
Most studies did not report clearly the interval between the last dose of anti-TNFα therapy and surgery. Several studies included patients within a peri-operative infliximab group if they had received the last dose within the 12 weeks of surgery. The study by Waterman et al. found no difference in outcomes whether anti-TNFα therapy was given in the 14 days preceding surgery vs. 15–30 days before surgery or 31–180 days before surgery. It is noteworthy that most studies have evaluated the effect of infliximab, and it is not clear whether surgical outcomes are similar after treatment with other inhibitors of TNFα.
Large, prospective, randomised, placebo-controlled, clinical trials will be needed to clarify the true benefits and risks of continuing anti-TNFα therapy in the peri-operative period. This meta-analysis suggests that recent exposure to anti-TNFα therapies in patients with IBD is associated with small increases in post-operative infectious, non-infectious and total post-operative complications. However, the small increase in apparent risk may well reflect residual confounding rather than true cause and effect. Interruption of therapy can reactivate IBD and/or promote the formation of neutralising antibodies. Furthermore, Waterman et al. suggest that increasing the time interval between the last dose of biological therapy and surgery does not lower the risk of post-operative infection. Accordingly, our data are insufficient to justify pre-operative interruption of biological therapy. Clinicians managing patients with IBD must continue to make individual decisions that are cognizant of these trade-offs in potential risk.
Discussion
The results of this meta-analysis suggest that peri-operative treatment with anti-TNFα medications modestly increases the post-operative risk of infectious, non-infectious and total complications in patients with IBD. These conclusions are similar to those of other systematic reviews. A recent meta-analysis found a statistically significant increased risk of infectious complications (OR 1.50, 95% CI 1.08–2.08), and a nonsignificant trends towards increased non-infectious (OR 2.00, 95% CI 0.89–4.46) and overall complications (OR 1.72, 95% CI 0.93–3.19) among patients with CD undergoing abdominal surgery. Another found no increased risk of infectious (OR 1.10, 95% 0.51–2.38), non-infectious (OR 1.10, 95% CI 0.76–1.59), or total complications (OR 1.09, 95% CI 0.87–1.37) among patients with UC treated preoperatively with infliximab. Our meta-analysis is the first to include data from mixed cohorts of IBD patients. We also include more recently published manuscripts and excluded lower quality studies.
There are several limitations to the current meta-analysis. Of all eligible studies, only one assessed outcomes prospectively. Observational studies cannot control for all potential confounding factors, and this is even more challenging with retrospective designs. Only a few studies adjusted for concurrent immunosuppressive use and age. Other factors such as disease severity and the nature, indication and timing of surgery may also influence outcome and patients treated with anti-TNFα therapies are more likely to have severe disease. Notably, seven studies that reported increased risks of infectious complications also reported higher concurrent use of immunomodulators or corticosteroids in the group treated peri-operatively with infliximab. Accordingly, increases in the rate of complications may reflect differences in morbidity rather than an effect of anti-TNFα therapy.
Most studies reported both infectious and non-infectious complications. Where it was not stated clearly whether these outcomes were mutually exclusive, we contacted the authors for clarification. Waterman et al. provided detailed information about subjects who experienced more than one complication, and our analysis accounts for this. However, Appau et al. did not respond to our inquiry and we analysed their data as reported. Sensitivity analysis showed that exclusion of these data did not affect the findings of our meta-analysis. There is also variability among studies in definitions of infectious and non-infectious complications. We accepted the original authors' classification but, where this was not provided, classified outcomes based on the data provided. The classification of different outcomes is detailed in Table S1.
Most studies did not report clearly the interval between the last dose of anti-TNFα therapy and surgery. Several studies included patients within a peri-operative infliximab group if they had received the last dose within the 12 weeks of surgery. The study by Waterman et al. found no difference in outcomes whether anti-TNFα therapy was given in the 14 days preceding surgery vs. 15–30 days before surgery or 31–180 days before surgery. It is noteworthy that most studies have evaluated the effect of infliximab, and it is not clear whether surgical outcomes are similar after treatment with other inhibitors of TNFα.
Large, prospective, randomised, placebo-controlled, clinical trials will be needed to clarify the true benefits and risks of continuing anti-TNFα therapy in the peri-operative period. This meta-analysis suggests that recent exposure to anti-TNFα therapies in patients with IBD is associated with small increases in post-operative infectious, non-infectious and total post-operative complications. However, the small increase in apparent risk may well reflect residual confounding rather than true cause and effect. Interruption of therapy can reactivate IBD and/or promote the formation of neutralising antibodies. Furthermore, Waterman et al. suggest that increasing the time interval between the last dose of biological therapy and surgery does not lower the risk of post-operative infection. Accordingly, our data are insufficient to justify pre-operative interruption of biological therapy. Clinicians managing patients with IBD must continue to make individual decisions that are cognizant of these trade-offs in potential risk.
Source...