The effect of appendectomy on the clinical course of ulcerative colitis: a synopsis of the ACCURE randomised controlled trial

Background Chronic relapsing diseases, such as ulcerative colitis, incur considerable long-term health burden to the patient and the state. Early interventions that reduce the rate of relapse could provide considerable benefits to patients and the health service. Research has shown that the appendix affects the development and activity of ulcerative colitis. Several small studies in patients with ulcerative colitis have found that appendicectomy might reduce disease relapse, hospitalisation and medication usage, with the potential to prevent the need for future major surgery. This intervention warranted further prospective and randomised investigation. Objective To assess the clinical effectiveness of laparoscopic appendicectomy in maintaining remission in adult patients with ulcerative colitis. Design An international randomised controlled trial. Setting and participants Participants were recruited from 21 hospitals across the Netherlands, Ireland and the United Kingdom. Eligible participants had established ulcerative colitis with a disease flare within the preceding 12 months but in confirmed stable remission at trial entry. Interventions Participants were randomly assigned in a 1 : 1 ratio to undergo laparoscopic appendicectomy and continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone (control group). Main outcome measures The primary outcome was the relapse rate at 1 year, defined as a total Mayo score ≥ 5 with endoscopic subscore of 2 or 3. Secondary outcomes included time-to-first relapse, number of relapses per patient, disease activity, number of colectomies, medication use and health-related quality of life over the 12-month follow-up period. Results Between 2012 and 2022, a total of 197 eligible participants were randomised; 99 were assigned to appendicectomy and 98 to control. At baseline, the mean (± standard deviation) age was 42.7 ± 12.7 years, median disease duration 5.1 years (interquartile range 1.7–11.3). Ulcerative colitis disease extent was 39.1% proctitis, 35.5% left-sided colitis and the remainder pancolitis. The 1-year relapse rate was significantly lower in the appendicectomy group compared to control [36.4% vs. 56.1%; relative risk 0.65 (95% confidence interval 0.47 to 0.89); p = 0.005, adjusted p = 0.002)]. Secondary outcome measures also favoured the appendicectomy group, including a longer time-to-first relapse (p = 0.003), a lower total Mayo score (p = 0.02), less initiation of biologics (p = 0.01) and higher inflammatory bowel disease-related quality of life (Inflammatory Bowel Disease Questionnaire; p = 0.006). There were two surgery-related serious adverse events (2.1%). Limitations The long trial duration, secondary to challenges in identifying eligible participants due to background changes in availability of medical therapy, then further compounded by the pandemic, may have affected external validity. The open-label design could have introduced reporting bias, specifically in relation to subjective end points. Conclusions Appendicectomy is an effective and safe intervention in the maintenance of remission in patients with ulcerative colitis, resulting in lower 1-year relapse rates compared to standard care. In addition to this, those undergoing appendicectomy experienced less disease flares overall, a prolonged time to flare, lower disease activity scores, less escalation of medication and improved quality of life. Future work Now it has been shown to be effective, more work is needed to establish how appendicectomy works, its longer-term effects beyond 1 year, and whether it may also have a beneficial role in active ulcerative colitis. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 16/61/35. Plain language summary Why did we do this trial? Ulcerative colitis is a chronic inflammatory bowel disease affecting around 150,000 people in the United Kingdom. Around 40% of ulcerative colitis sufferers experience a relapse or flare of their disease each year, with pain, bleeding and debilitating diarrhoea. Reducing the rate and severity of disease flares is a priority for patients. Previous research suggests that the appendix may play a role in ulcerative colitis. We aimed to establish whether a minor operation to remove the appendix (called an appendicectomy) improves symptoms in patients with ulcerative colitis. What did we do? This project funded the United Kingdom portion of an international trial undertaken in collaboration with colleagues in the Netherlands. Between September 2012 and September 2022, a total of 197 patients with ulcerative colitis who had experienced a flare in the preceding year, but were currently in remission, were recruited from across both countries. These trial participants were randomly assigned to receive either an appendicectomy operation and continue their standard medical treatment or continue on their standard medical treatment alone. They were closely followed up for 12 months to capture information on disease activity, medication use, hospital visits and quality of life. What did we find? Patients who underwent appendicectomy experienced significantly lower rates of disease activity over the following 12-month period. These participants had less disease flares overall, and the time-to-first relapse was significantly longer compared to the control group. They also had lower overall disease activity scores, less need for medication increases and improved quality-of-life scores. What does this mean for patients with ulcerative colitis? An appendicectomy was effective in improving the disease activity of patients with ulcerative colitis over the following year. This simple operation was safe and well tolerated. It may represent a new treatment option for those suffering from ulcerative colitis.