Brigida Barberio

Credit: ResearchGate

Trial design is crucial in evaluating remission rates for patients with inflammatory bowel disease (IBD).¹

A team, led by Brigida Barberio, Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, evaluated results of IBD trials based on trial design.

Trials

Randomized controlled trials looking at the maintenance of clinical remission in patients with IBD can vary greatly. Some trials rerandomize patients who have responded to active drugs during induction to either active drugs or placebo. Other treat patients through active drug or placebo from baseline.

However, it is unknown whether this influences therapeutic gain of drug over placebo.

“Despite the availability of a range of therapies for IBD, achieving sustained remission for all patients remains elusive, with most existing treatments exhibiting maintenance of remission rates of approximately 30% to 40% at 12 months,” the authors wrote.

In addition, in recent years trial designs have evolved to become increasingly complex and sophisticated with new endpoints that could include patient-reported outcomes, biomarkers, mucosal, and histological healing, central endoscopy reading, and trials that examine both induction and maintenance of remission within the same study.

The Study

In the study, the investigators searched databases to January 2023 for maintenance of remission trials of biologics or small molecules compared to placebo for patients with IBD. The investigators extracted maintenance of remission rates by trial design. This included either trials re-randomizing patients or trials treating patients through.

The investigators pooled data in a meta-analysis of all patients, as well as according to type of IBD. They also calculated the number needed to treat to assess therapeutic gain of active drug over placebo according to trial design.

Overall, there were 37 maintenance of remission trials involving 12,075 patients with IBD included in the study.

The results show a rate of maintenance of clinical remission was higher (41.9% with active drug, versus 20.3% with placebo) in trials re-randomizing patients compared to trials treating through (maintenance of remission rate 30.9% with active drug versus 14.6% with placebo).

The NNT was also lowest in trials re-randomizing patients (NNT = 5; 95% confidence interval [CI], 4–6) compared to those treating through (NNT = 7; 95% CI, 5–9).

The results were similar in trials that were analyzed by IBD type. However, they were more marked in ulcerative colitis randomized controlled trials (maintenance of remission rates in re-randomized trials 39.4% with active drug versus 17.8% with placebo, NNT = 5; 95% CI 3–7; treat-through trials 27.3% with active drug versus 11.9% with placebo, NNT = 7; 95% CI 5–11.5).

“Trials re-randomizing patients had generally higher maintenance of remission rates, lower NNTs, and greater therapeutic gains over placebo,” the authors wrote.

References:

Barberio, B., Gracie, D. J., Black, C. J., & Ford, A. C. (2023). Maintenance of clinical remission with biologics and small molecules in inflammatory bowel disease according to trial design: Meta-analysis. Digestive and Liver Disease. https://doi.org/10.1016/j.dld.2023.06.009