Observational versus antibiotic therapy for acute uncomplicated diverticulitis: A non-inferiority meta-analysis based on a Delphi consensus

Abstract

Background: The purpose of this study was to determine if observational therapy is noninferior to antibiotics for acute uncomplicated diverticulitis according to clinically relevant margins.

Methods: MEDLINE, EMBASE, and Cochrane were systematically searched by 2 independent reviewers to identify comparative studies of observational therapy versus antibiotics for acute uncomplicated diverticulitis. Non-inferiority margins (ΔNI) for each outcome were based on Delphi consensus including 50 patients and 55 physicians: persistent diverticulitis (ΔNI = 4.0%), progression to complicated diverticulitis (ΔNI = 3.0%), and time to recovery (ΔNI = 5 days). Risk differences and mean differences were pooled using random-effects meta-analysis. One-sided 90% confidence intervals and Z-tests were used to determine non-inferiority. A sensitivity analysis was performed, excluding patients post hoc determined to have complicated diverticulitis.

Results: Nine studies (3 randomized controlled trials, 6 observational studies) met inclusion criteria: observational therapy (n = 2,011) versus antibiotics (n = 1,144). Observational therapy was noninferior to antibiotics regarding the risk of persistent diverticulitis (pooled risk differences: -0.39%, 90% CI -3.22 to 2.44%, ΔNI: 4.0%, P_NI < 0.001; I² = 66%) and progression to complicated diverticulitis (pooled risk differences: -0.030%, 90% CI -0.99 to 0.92%, ΔNI: 3.0%, P_NI < 0.001; I² = 0%). On sensitivity analysis, observational therapy remained noninferior for both outcomes. When stratified by study design, observational therapy also remained noninferior for both outcomes among randomized controlled trials only. Only 1 study reported on time to recovery as a continuous outcome, with no statistical difference between antibiotics and observational therapy.

Conclusion: According to clinically relevant ΔNIs, observational therapy was noninferior to antibiotics for the treatment of acute uncomplicated diverticulitis with regard to persistent diverticulitis and progression to complicated diverticulitis.