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Acute appendicitis treated with antibiotics often ends up being treated with appendectomy, longer-term follow-up of the CODA Collaborative trial showed.

In the antibiotics group, 40% had surgery to remove their appendix by 1 year, which rose to 46% by year 2, reported David Flum, MD, MPH, of the University of Washington in Seattle, and colleagues.

Patients with an appendicolith faced particularly high risk of subsequent surgery, they noted in a in the New England Journal of Medicine in conjunction with their presentation at the .

Among patients with these calcified accumulations of fecal matter, about 50% needed appendectomy within 1 year compared with about 40% of other patients treated with antibiotics. However, the risk dropped off rapidly with time, from a hazard ratio of 2.9 at 48 hours, to a nonsignificant 1.4 at 30 days, and then to 1.1 beyond that.

"Although some clinicians and patients may determine that these longer-term rates of appendectomy make antibiotics a less desirable treatment than early appendectomy, substantial numbers of patients report a preference for antibiotics, even if appendectomy may ultimately be necessary," the group cautioned.

Either way, "the present data will further inform shared decision making between clinicians and their patients with appendicitis, including those with an appendicolith," they concluded.

In the initial results from the trial, the primary outcome of 30-day health status showed antibiotics to be noninferior to appendectomy and similar 1-week resolution of appendicitis symptoms, with 29% of the antibiotics group heading to surgery by 90 days.

The open-label included 1,552 consecutive acute appendicitis patients seen at the emergency department of 25 U.S. centers from May 2016 to February 2020. They were randomized to antibiotics (given via IV for at least 24 hours, followed by pills for the remainder of the 10-day course) or immediate appendectomy (laparoscopic in 96%).

For the subsequent follow-up, 82% of the participants had data for more than 2 years, 44% for more than 3 years, and 15% for more than 4 years.

Recurrent appendicitis, defined as the need for appendectomy for clinical reasons as the primary indication, occurred in 333 patients initially randomized to antibiotics. Nearly all with a pathology report available had appendicitis confirmed in it (94% of 297).

"In our trial, the longer-term incidence of appendectomy in the antibiotics group was higher than pooled results from prior trials," Flum's group noted. "This finding is probably related to our inclusion of patients with radiographic evidence of an appendicolith or perforation, common findings in patients with appendicitis."

Unlike many previous studies, CODA enrolled 414 patients with .

One of the initial concerns was the increased rate of complications with antibiotic treatment, which was 2.28-fold higher compared with the surgery group. In the extended follow-up data, complications were "uncommon" beyond 30 days, even for the appendicolith patients. Perforation was statistically similar between treatment groups among those who had an appendicitis recurrence, with a 20% rate in the antibiotics group and a 16% rate in the appendectomy group.

Limitations to the study included the low rate of follow-up beyond 2 years, making those results less reliable, as well as the somewhat arbitrary definition of the window for recurrence. Importantly, patients who were prescribed an additional course of antibiotics but didn't undergo surgery didn't count as recurrences, "because appendicitis could not be confirmed."

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