Triple combo therapy in CD

August 30, 2024

Issue 17

Clinical Question

Is triple combination therapy safe and effective in patients with CD with moderate-to-high risk of complications?

Editor’s Bottom Line

Combination therapy was associated with reasonable efficacy and no concerning safety signals. With growing interest in such strategies, controlled trials are needed.

Reference

Colombel J-F, Ungaro RC, Sands BE. Vedolizumab, adalimumab, and methotrexate combination therapy in Crohn’s disease. Clinical Gastroenterol Hepatol 2024;22:1487–96. https://www.cghjournal.org/article

Synopsis

A Phase 4, prospective, single-arm, open-label study on the safety and efficacy of triple combination therapy in Crohn’s disease (CD). Triple combination therapy consisted of vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly).

The study included biologic-naïve patients with newly diagnosed (within 24 months), moderate-to high-risk CD based on a centrally assessed Simple Endoscopic Score for Crohn’s Disease (SES-CD) of ≥7 or higher (or ≥4 for isolated ileal disease).

Among 55 enrolled patients, the mean age was 32.4 years, and 56.4% were male. The mean CD duration was 0.4 years, mean baseline SES-CD was 12.6, and mean baseline Crohn’s Disease Activity Index (CDAI) was 265.5. Of those enrolled, 80.0% completed treatment.

The results for the primary endpoint revealed an endoscopic remission rate (SES-CD 0-2) of 34.5% at week 26. The secondary endpoint of clinical remission at weeks 10 and 26 (CDAI <150) showed rates of 61.8% and 54.5%, respectively.

Post hoc Bayesian analysis determined that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4–45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%), were 99.9% or higher, 86.3%, and 71.4%, respectively.

During the triple combination therapy phase of the study, 26 adverse events (AEs) in 17 patients (30.9%) were considered to be related to the study drug, and most were classified as mild or moderate. Eight serious AEs occurred in six patients, of these three AEs in two patients were considered related to the treatment regimen, and one led to treatment discontinuation.

Details

Study Design: prospective, single-arm, open label
Funding: Takeda Pharmaceuticals U.S.A., Inc, and National Institutes of Health K23 Career Development Award
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2b